Geographic variation in sexual behavior can explain geospatial heterogeneity in the severity of the HIV epidemic in Malawi.

BACKGROUND: In sub-Saharan Africa, where ~ 25 million individuals are infected with HIV and transmission is predominantly heterosexual, there is substantial geographic variation in the severity of epidemics. This variation has yet to be explained. Here, we propose that it is due to geographic variation in the size of the high-risk group (HRG): the group with a high number of sex partners. We test our hypothesis by conducting a geospatial analysis of data from Malawi, where ~ 13% of women and ~ 8% of men are infected with HIV. METHODS: We used georeferenced HIV testing and behavioral data from ~ 14,000 participants of a nationally representative population-level survey: the 2010 Malawi Demographic and Health Survey (MDHS). We constructed gender-stratified epidemic surface prevalence (ESP) maps by spatially smoothing and interpolating the HIV testing data. We used the behavioral data to construct gender-stratified risk maps that reveal geographic variation in the size of the HRG. We tested our hypothesis by fitting gender-stratified spatial error regression (SER) models to the MDHS data. RESULTS: The ESP maps show considerable geographic variation in prevalence: 1-29% (women), 1-20% (men). Risk maps reveal substantial geographic variation in the size of the HRG: 0-40% (women), 16-58% (men). Prevalence and the size of the HRG are highest in urban centers. However, the majority of HIV-infected individuals (~75% of women, ~ 80% of men) live in rural areas, as does most of the HRG (~ 80% of women, ~ 85% of men). We identify a significant (P < 0.001) geospatial relationship linking the size of the HRG with prevalence: the greater the size, the higher the prevalence. SER models show HIV prevalence in women is expected to exceed the national average in districts where > 20% of women are in the HRG. Most importantly, the SER models show that geographic variation in the size of the HRG can explain a substantial proportion (73% for women, 67% for men) of the geographic variation in epidemic severity. CONCLUSIONS: Taken together, our results provide substantial support for our hypothesis. They provide a potential mechanistic explanation for the geographic variation in the severity of the HIV epidemic in Malawi and, potentially, in other countries in sub-Saharan Africa.

Modelling the effects of calcium waves and oscillations on saliva secretion.

An understanding of Ca(2+) signalling in saliva-secreting acinar cells is important, as Ca(2+) is the second messenger linking stimulation of cells to production of saliva. Ca(2+) signals affect secretion via the ion channels located both apically and basolaterally in the cell. By approximating Ca(2+) waves with periodic functions on the apical and basolateral membranes, we isolate individual wave properties and investigate them for their effect on fluid secretion in a mathematical model of the acinar cell. Mean Ca(2+) concentration is found to be the most significant property in signalling secretion. Wave speed was found to encode a range of secretion rates. Ca(2+) oscillation frequency and amplitude had little effect on fluid secretion.

A dynamic model of saliva secretion.

We construct a mathematical model of the parotid acinar cell with the aim of investigating how the distribution of K(+) and Cl(-) channels affects saliva production. Secretion of fluid is initiated by Ca(2+) signals acting on Ca(2+) dependent K(+) and Cl(-) channels. The opening of these channels facilitates the movement of Cl(-) ions into the lumen which water follows by osmosis. We use recent results into both the release of Ca(2+) from internal stores via the inositol (1,4,5)-trisphosphate receptor (IP(3)R) and IP(3) dynamics to create a physiologically realistic Ca(2+) model which is able to recreate important experimentally observed behaviours seen in parotid acinar cells. We formulate an equivalent electrical circuit diagram for the movement of ions responsible for water flow which enables us to calculate and include distinct apical and basal membrane potentials to the model. We show that maximum saliva production occurs when a small amount of K(+) conductance is located at the apical membrane, with the majority in the basal membrane. The maximum fluid output is found to coincide with a minimum in the apical membrane potential. The traditional model whereby all Cl(-) channels are located in the apical membrane is shown to be the most efficient Cl(-) channel distribution.

Travel time to health-care facilities, mode of transportation, and HIV elimination in Malawi: a geospatial modelling analysis.

BACKGROUND: UNAIDS has prioritised Malawi and 21 other countries in sub-Saharan Africa for fast-tracking the end of their HIV epidemics. UNAIDS' elimination strategy requires achieving a treatment coverage of 90% by 2030. However, many individuals in the prioritised countries have to travel long distances to access HIV treatment and few have access to motorised transportation. Using data-based geospatial modelling, we investigated whether these two factors are barriers to achieving HIV elimination in Malawi and assessed the effect of increasing bicycle availability on expanding treatment coverage. METHODS: We built a data-based geospatial model that we used to estimate the minimum travel time needed to access treatment, for every person living with HIV in Malawi. We constructed our model by combining a spatial map of health-care facilities, a map that showed the number of HIV-infected individuals per km2, and an impedance map. We quantified impedance using data on road and river networks, land cover, and topography. We estimated travel times for the existing coverage of 70%, and the time that HIV-infected individuals would need to spend travelling in order to achieve a coverage of 90%, whether driving, bicycling, or walking. FINDINGS: We identified a quantitative relationship between the maximum achievable coverage of treatment and the minimum travel time to the nearest health-care facility. At 70% coverage, health-care facilities can be reached within approximately 45 min if driving, 65 min if bicycling, and 85 min if walking. Increasing coverage above 70% will become progressively more difficult. To reach 90% coverage, many HIV-infected individuals (who have yet to initiate treatment) will need to travel for almost twice as long as those already on treatment. Bicycling, rather than walking, in rural areas would substantially increase the maximum achievable coverage. INTERPRETATION: The long travel times needed to reach health-care facilities coupled with little motorised transportation in rural areas are substantial barriers to reaching 90% coverage in Malawi. Increased bicycle availability could help eliminate HIV. FUNDING: US National Institute of Allergy and Infectious Diseases.

HIV transmission and source-sink dynamics in sub-Saharan Africa.

Multiple phylogenetic studies of HIV in sub-Saharan Africa have shown that mobility-driven transmission frequently occurs: many communities export and import strains. Mobility-driven transmission can result in source-sink dynamics: one community can sustain a micro-epidemic in another community in which transmission is too low to be self-sustaining. In epidemiology, the basic reproduction number (R0) is used to specify the sustainability threshold. R0 represents the average number of secondary infections generated by one infected individual in a community in which everyone is susceptible. If R0 is greater than 1, transmission is high enough to sustain an epidemic; if R0 is less than 1, it is not. Here, we discuss the conditions that are needed (in terms of R0) for source-sink transmission dynamics to occur in generalised HIV epidemics in sub-Saharan Africa, present an example of where these conditions could occur (ie, Namibia), and discuss the necessity of considering mobility-driven transmission when designing control strategies. Additionally, we discuss the need for a new generation of HIV transmission models that are more realistic than the current models. The new models should reflect not only geographical variation in epidemiology and demography, but also the spatial-temporal complexity of population-level movement patterns.

A modeling study of the Danish HIV epidemic in men who have sex with men: travel, pre-exposure prophylaxis and elimination.

UNAIDS has identified the Danish HIV epidemic in men who have sex with men (MSM) as a priority for elimination. Incidence is close to the elimination threshold of one new infection per year per 1,000 individuals. However, surveillance data show that HIV strains are being imported into Denmark, mainly due to travel. We use a transmission model to predict (from 2018 to 2030) the impact of pre-exposure prophylaxis (PrEP) on incidence. Our model reflects the current epidemic and diagnosis rates in the Danish MSM community. We conduct a sensitivity analysis based on 20,000 simulations, and assume that PrEP coverage could range from zero to 50% and diagnosis rates increase up to three-fold. We predict that incidence will fall below the elimination threshold, even without the introduction of PrEP, reaching 0.87 (median, 95% Confidence Interval: 0.65-1.23) new infections per 1,000 MSM by 2030. PrEP could reduce incidence to well below the threshold, if it results in a significant increase in diagnosis rates and reduces the number of infections occurring abroad. The Danish Medicine Agency and Danish Health Authority have recommended introducing PrEP. Our study provides strong support for this recommendation, and shows the importance of Danish MSM using PrEP when abroad.

Testing the hypothesis that treatment can eliminate HIV: a nationwide, population-based study of the Danish HIV epidemic in men who have sex with men.

BACKGROUND: Worldwide, approximately 35 million individuals are infected with HIV; about 25 million of these live in sub-Saharan Africa. WHO proposes using treatment as prevention (TasP) to eliminate HIV. Treatment suppresses viral load, decreasing the probability an individual transmits HIV. The elimination threshold is one new HIV infection per 1000 individuals. Here, we test the hypothesis that TasP can substantially reduce epidemics and eliminate HIV. We estimate the impact of TasP, between 1996 and 2013, on the Danish HIV epidemic in men who have sex with men (MSM), an epidemic UNAIDS has identified as a priority for elimination. METHODS: We use a CD4-staged Bayesian back-calculation approach to estimate incidence, and the hidden epidemic (the number of HIV-infected undiagnosed MSM). To develop the back-calculation model, we use data from an ongoing nationwide population-based study: the Danish HIV Cohort Study. FINDINGS: Incidence, and the hidden epidemic, decreased substantially after treatment was introduced in 1996. By 2013, incidence was close to the elimination threshold: 1·4 (median, 95% Bayesian credible interval [BCI] 0·4-2·1) new HIV infections per 1000 MSM and there were only 617 (264-858) undiagnosed MSM. Decreasing incidence and increasing treatment coverage were highly correlated; a treatment threshold effect was apparent. INTERPRETATION: Our study is the first to show that TasP can substantially reduce a country's HIV epidemic, and bring it close to elimination. However, we have shown the effectiveness of TasP under optimal conditions: very high treatment coverage, and exceptionally high (98%) viral suppression rate. Unless these extremely challenging conditions can be met in sub-Saharan Africa, the WHO's global elimination strategy is unlikely to succeed. FUNDING: National Institute of Allergy and Infectious Diseases.

Mapping divided households and residency changes: the effect of couple separation on sexual behavior and risk of HIV infection.

Using census data we identify geographic patterns in residency changes in Lesotho over a decade. Using kriging to spatially interpolate data from 8,510 households we identify regions where households have members temporarily living away from home (divided households). Further, using a multivariate analysis and data from 2,026 couples we determine whether a partners' absence increases the likelihood of having extramarital partners and/or risk of HIV infection. Approximately 40% of individuals moved between 2001 and 2011; mainly to, and within, urbanized regions. Many households are divided: ~40% have members elsewhere in Lesotho, ~30% in South Africa (SA). Geographic patterns are apparent; they differ based on where the household member is living. Many couples were temporarily separated: ~50% of wives, ~20% of husbands. Separation was not a risk factor for HIV. Only men were more likely to have extramarital partners if their spouse was away: ~1.5 times if in Lesotho, ~3 times if in SA. The high degree of geographic mixing necessitates synchronizing interventions within Lesotho, and with SA, to successfully reduce transmission. It will be challenging to reduce concurrency in men with wives away from home. Our results are generalizable to other sub-Saharan countries where residency changes are common.

Brief report: Mobility and circular migration in Lesotho: implications for transmission, treatment, and control of a severe HIV epidemic.

We analyzed georeferenced data on mobility and HIV infection from the 2009 Demographic and Health Survey of Lesotho. We found ∼50% of the population traveled in the preceding year. By constructing gender-specific mobility maps, we discovered that travel is highest in the urban areas bordering South Africa and in the mountainous interior of the country. For both genders, increased mobility was associated with increased levels of "recent" sexual behavior. Notably, mobility was only associated with an increased risk of HIV infection for men who traveled frequently. We discuss the implications of our results for designing effective treatment programs and HIV interventions.