Merge pull request #70 from UCL/stp-HIV-transmission

WIP: HIV transmission for short term partners

src/hivpy/column_names.py

@@ -15,11 +15,14 @@
 RRED_ART_ADHERENCE = "rred_art_adherence"   # float: risk reduction associated with low ART adherence
 RRED_INTIIAL = "rred_initial"               # float: initial risk reduction factor
 NUM_PARTNERS = "num_partners"               # float: number of short term condomless sex partners during the current time step
+SEX_MIX_AGE_GROUP = "sex_mix_age_group"     # int: Discrete age group for sexual mixing
+STP_AGE_GROUPS = "stp_age_groups"           # int array: ages groups of short term partners
 SEX_BEHAVIOUR = "sex_behaviour"             # int: sexual behaviour grouping
 LONG_TERM_PARTNER = "long_term_partner"     # bool: True if the subject has a long term condomless partner
 LTP_LONGEVITY = "ltp_longevity"             # int: categorises longevity of long term partnerships (higher => more stable)
 
 HIV_STATUS = "HIV_status"                   # bool: true if person if HIV positive, o/w false
 HIV_DIAGNOSIS_DATE = "HIV_Diagnosis_Date"   # None | datetime.date: date of HIV diagnosis (to nearest timestep) if HIV+, o/w None
+VIRAL_LOAD_GROUP = "viral_load_group"       # int: value 1-6 placing bounds on viral load for an HIV positive person
 
 DATE_OF_DEATH = "date_of_death"             # None | datetime.date: date of death if dead, o/w None

src/hivpy/common.py

@@ -16,6 +16,7 @@ def __init__(self, vals: np.ndarray, probs):
         if (len(probs) != N):
             raise Exception
         index_range = np.arange(0, N, 1)
+        self.probs = probs
         self.data = vals
         self.dist = stat.rv_discrete(values=(index_range, probs))
 
@@ -36,6 +37,10 @@ class SexType(IntEnum):
     Female = 1
 
 
+def opposite_sex(sex: SexType):
+    return (1 - sex)
+
+
 def diff_years(date_begin, date_end):
     return (date_end - date_begin) / datetime.timedelta(days=365.25)
 

src/hivpy/hiv_status.py

@@ -1,17 +1,34 @@
-import operator
-
+import numpy as np
 import pandas as pd
 
 import hivpy.column_names as col
 
-from .common import rng
-from .sexual_behaviour import selector
+from .common import SexType, opposite_sex, rng
 
 
 class HIVStatusModule:
     initial_hiv_newp_threshold = 7  # lower limit for HIV infection at start of epidemic
     initial_hiv_prob = 0.8  # for those with enough partners at start of epidemic
 
+    def __init__(self):
+        self.stp_HIV_rate = {SexType.Male: np.zeros(5),
+                             SexType.Female: np.zeros(5)}  # FIXME
+        self.stp_viral_group_rate = {SexType.Male: np.array([np.zeros(7)]*5),
+                                     SexType.Female: np.array([np.zeros(7)]*5)}
+        # FIXME move these to data file
+        # a more descriptive name would be nice
+        self.fold_tr_newp = rng.choice(
+            [0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1/0.8, 1/0.6, 1/0.4])
+        self.fold_change_w = rng.choice([1., 1.5, 2.], p=[0.05, 0.25, 0.7])
+        self.fold_change_yw = rng.choice([1., 2., 3.]) * self.fold_change_w
+        self.fold_change_sti = rng.choice([2., 3.])
+        self.tr_rate_primary = 0.16
+        self.tr_rate_undetectable_vl = rng.choice([0.0000, 0.0001, 0.0010], p=[0.7, 0.2, 0.1])
+        self.transmission_means = self.fold_tr_newp * \
+            np.array([0, self.tr_rate_undetectable_vl, 0.01, 0.03, 0.06, 0.1, self.tr_rate_primary])
+        self.transmission_sigmas = np.array(
+            [0, 0.000025**2, 0.0025**2, 0.0075**2, 0.015**2, 0.025**2, 0.075**2])
+
     def initial_HIV_status(self, population: pd.DataFrame):
         """Initialise HIV status at the start of the simulation to no infections."""
         # This may be useful as a separate method if we end up representing status
@@ -29,17 +46,88 @@ def introduce_HIV(self, population: pd.DataFrame):
         hiv_status.loc[initial_candidates] = initial_infection
         return hiv_status
 
-    def update_HIV_status(self, population: pd.DataFrame):
+    def update_partner_risk_vectors(self, population):
+        """calculate the risk factor associated with each sex and age group"""
+        # Should we be using for loops here or can we do better?
+        for sex in SexType:
+            for age_group in range(5):   # FIXME need to get number of age groups from somewhere
+                sub_pop = population.data.loc[(population.data[col.SEX] == sex) & (
+                    population.data[col.SEX_MIX_AGE_GROUP] == age_group)]
+                # total number of people partnered to people in this group
+                n_stp_total = sum(sub_pop[col.NUM_PARTNERS])
+                # num people partered to HIV+ people in this group
+                n_stp_of_infected = sum(sub_pop.loc[sub_pop[col.HIV_STATUS], col.NUM_PARTNERS])
+                # Probability of being HIV prositive
+                if n_stp_of_infected == 0:
+                    self.stp_HIV_rate[sex][age_group] = 0
+                else:
+                    self.stp_HIV_rate[sex][age_group] = n_stp_of_infected / \
+                        n_stp_total  # TODO: need to double check this definition
+                # Chances of being in a given viral group
+                if n_stp_total > 0:
+                    self.stp_viral_group_rate[sex][age_group] = [
+                        sum(sub_pop.loc[sub_pop[col.VIRAL_LOAD_GROUP] == vg,
+                            col.NUM_PARTNERS])/n_stp_total for vg in range(7)]
+                else:
+                    self.stp_viral_group_rate[sex][age_group] = np.array([1, 0, 0, 0, 0, 0, 0])
+
+    def set_dummy_viral_load(self, population):
+        """Dummy function to set viral load until this
+        part of the code has been implemented properly"""
+        population.data[col.VIRAL_LOAD_GROUP] = rng.choice(7, population.size)
+
+    def get_infection_prob(self, sex, age, n_partners, stp_age_groups):
+        # Slow example that avoid repeating the iterations over partners
+        # three time by putting them as part of
+        # one for loop, but for loops in python will be slow.
+        target_sex = opposite_sex(sex)
+        infection_prob = np.zeros(n_partners)
+        for i in range(n_partners):
+            stp_viral_group = rng.choice(
+                7, p=self.stp_viral_group_rate[target_sex][stp_age_groups[i]])
+            HIV_probability = self.stp_HIV_rate[opposite_sex(target_sex)][stp_age_groups[i]]
+            infection_prob[i] = HIV_probability * max(0, rng.normal(
+                self.transmission_means[stp_viral_group],
+                self.transmission_sigmas[stp_viral_group]))
+            if (sex == SexType.Female):
+                if (age < 20):
+                    infection_prob[i] *= self.fold_change_yw
+                else:
+                    infection_prob[i] *= self.fold_change_w
+        return infection_prob
+
+    def stp_HIV_transmission(self, person):
+        # TODO: Add circumcision, STIs etc.
+        """Returns True if HIV transmission occurs, and False otherwise"""
+        stp_viral_groups = np.array([
+            rng.choice(7, p=self.stp_viral_group_rate[opposite_sex(person[col.SEX])][age_group])
+            for age_group in person[col.STP_AGE_GROUPS]])
+        HIV_probabilities = np.array([self.stp_HIV_rate[opposite_sex(
+            person[col.SEX])][age_group] for age_group in person[col.STP_AGE_GROUPS]])
+        viral_transmission_probabilities = np.array([max(0, rng.normal(
+            self.transmission_means[group], self.transmission_sigmas[group]))
+            for group in stp_viral_groups])
+        if person[col.SEX] is SexType.Female:
+            if person[col.AGE] < 20:
+                viral_transmission_probabilities = (viral_transmission_probabilities
+                                                    * self.fold_change_yw)
+            else:
+                viral_transmission_probabilities = (viral_transmission_probabilities
+                                                    * self.fold_change_w)
+        prob_uninfected = np.prod(1-(HIV_probabilities * viral_transmission_probabilities))
+        r = rng.random()
+        return r > prob_uninfected
+
+    def update_HIV_status(self, population):
         """Update HIV status for new transmissions in the last time period.\\
             Super simple model where probability of being infected by a given person
             is prevalence times transmission risk (P x r).\\
             Probability of each new partner not infecting you then is (1-Pr)\\
             Then prob of n partners independently not infecting you is (1-Pr)**n\\
             So probability of infection is 1-((1-Pr)**n)"""
-        HIV_neg_idx = selector(population, HIV_status=(operator.eq, False))
-        rands = rng.uniform(0.0, 1.0, sum(HIV_neg_idx))
-        HIV_prevalence = sum(population[col.HIV_STATUS])/len(population)
-        HIV_infection_risk = 0.2  # made up, based loosely on transmission probabilities
-        n_partners = population.loc[HIV_neg_idx, col.NUM_PARTNERS]
-        HIV_prob = 1-((1-HIV_prevalence*HIV_infection_risk)**n_partners)
-        population.loc[HIV_neg_idx, col.HIV_STATUS] = (rands <= HIV_prob)
+        self.update_partner_risk_vectors(population)
+        HIV_neg_idx = population.data.index[(~population.data[col.HIV_STATUS]) & (
+            population.data[col.NUM_PARTNERS] > 0)]
+        sub_pop = population.data.loc[HIV_neg_idx]
+        population.data.loc[HIV_neg_idx, col.HIV_STATUS] = sub_pop.apply(
+            self.stp_HIV_transmission, axis=1)

src/hivpy/population.py

@@ -58,6 +58,9 @@ def _create_population_data(self):
         self.sexual_behaviour.init_sex_behaviour_groups(self.data)
         self.sexual_behaviour.init_risk_factors(self.data)
         self.sexual_behaviour.num_short_term_partners(self)
+        self.sexual_behaviour.assign_stp_ages(self)
+        # TEMP
+        self.hiv_status.set_dummy_viral_load(self)
         # If we are at the start of the epidemic, introduce HIV into the population.
         if self.date >= HIV_APPEARANCE and not self.HIV_introduced:
             self.data[col.HIV_STATUS] = self.hiv_status.introduce_HIV(self.data)
@@ -101,7 +104,7 @@ def evolve(self, time_step: datetime.timedelta):
 
         # Get the number of sexual partners this time step
         self.sexual_behaviour.update_sex_behaviour(self)
-        self.hiv_status.update_HIV_status(self.data)
+        self.hiv_status.update_HIV_status(self)
 
         # If we are at the start of the epidemic, introduce HIV into the population.
         if self.date >= HIV_APPEARANCE and not self.HIV_introduced:

src/hivpy/sexual_behaviour.py

@@ -51,10 +51,20 @@ def __init__(self, **kwargs):
         self.risk_categories = len(self.age_based_risk)-1
         self.risk_min_age = 15  # This should come out of config somewhere
         self.risk_age_grouping = 5  # ditto
+        self.risk_max_age = 65
+        self.sex_mix_age_grouping = 10
+        self.sex_mix_age_groups = np.arange(self.risk_min_age,
+                                            self.risk_max_age,
+                                            self.sex_mix_age_grouping)
+        self.num_sex_mix_groups = len(self.sex_mix_age_groups)
+        self.age_limits = [self.risk_min_age + n*self.risk_age_grouping
+                           for n in range((self.risk_max_age - self.risk_min_age)
+                                          // self.risk_age_grouping)]
         self.sex_mixing_matrix = {
             SexType.Male: rng.choice(self.sb_data.sex_mixing_matrix_male_options),
             SexType.Female: rng.choice(self.sb_data.sex_mixing_matrix_female_options)
         }
+        # FIXME we don't have the over25 distribution here!
         self.short_term_partners = {SexType.Male: self.sb_data.male_stp_dists,
                                     SexType.Female: self.sb_data.female_stp_u25_dists}
         self.ltp_risk_factor = self.sb_data.rred_long_term_partnered.sample()
@@ -88,6 +98,7 @@ def age_index(self, age):
 
     def update_sex_behaviour(self, population):
         self.num_short_term_partners(population)
+        self.assign_stp_ages(population)
         self.update_sex_groups(population)
         self.update_rred(population)
         self.update_long_term_partners(population)
@@ -130,7 +141,7 @@ def num_short_term_partners(self, population):
         active_pop = population.data.index[(15 <= population.data.age) & (population.data.age < 65)]
         num_partners = population.transform_group(
             [col.SEX, col.SEX_BEHAVIOUR], self.get_partners_for_group, sub_pop=active_pop)
-        population.data.loc[active_pop, col.NUM_PARTNERS] = num_partners
+        population.data.loc[active_pop, col.NUM_PARTNERS] = num_partners.astype(int)
 
     def _assign_new_sex_group(self, sex, group, rred, size):
         group = int(group)
@@ -286,6 +297,24 @@ def update_rred_balance(self, population):
             population.loc[men, col.RRED_BALANCE] = 1/rred_balance
             population.loc[women, col.RRED_BALANCE] = rred_balance
 
+    def gen_stp_ages(self, sex, age_group, num_partners, size):
+        # TODO: Check if this needs additional balancing factors for age
+        stp_age_probs = self.sex_mixing_matrix[sex][age_group]
+        stp_age_groups = rng.choice(self.num_sex_mix_groups, [size, num_partners], p=stp_age_probs)
+        return list(stp_age_groups)  # dataframe won't accept a 2D numpy array
+
+    def assign_stp_ages(self, population):
+        """Calculate the ages of a persons short term partners
+        from the mixing matrices."""
+        population.data[col.SEX_MIX_AGE_GROUP] = np.digitize(
+            population.data[col.AGE], self.sex_mix_age_groups) - 1
+        # only select people with STPs
+        active_pop = population.data.index[population.data[col.NUM_PARTNERS] > 0]
+        STP_groups = population.transform_group([col.SEX, col.SEX_MIX_AGE_GROUP, col.NUM_PARTNERS],
+                                                self.gen_stp_ages,
+                                                sub_pop=active_pop)
+        population.data.loc[active_pop, col.STP_AGE_GROUPS] = STP_groups
+
     def update_ltp_rate_change(self, date):
         if date1995 < date < date2000:
             dt = diff_years(date1995, date)

src/tests/test_hiv_status.py

@@ -6,6 +6,7 @@
 import pytest
 
 import hivpy.column_names as col
+from hivpy.common import SexType
 from hivpy.hiv_status import HIVStatusModule
 from hivpy.population import Population
 from hivpy.sexual_behaviour import selector
@@ -90,7 +91,7 @@ def test_hiv_update(pop_with_initial_hiv):
     data = pop_with_initial_hiv.data
     prev_status = data["HIV_status"].copy()
     for i in range(10):
-        pop_with_initial_hiv.hiv_status.update_HIV_status(pop_with_initial_hiv.data)
+        pop_with_initial_hiv.hiv_status.update_HIV_status(pop_with_initial_hiv)
 
     new_cases = data["HIV_status"] & (~ prev_status)
     print("Num new HIV+ = ", sum(new_cases))
@@ -99,3 +100,94 @@ def test_hiv_update(pop_with_initial_hiv):
     assert not any(miracles)
     assert any(new_cases)
     assert not any(under_15s_idx)
+
+
+def test_HIV_risk_vector():
+    N = 10000
+    pop = Population(size=N, start_date=date(1989, 1, 1))
+    hiv_module = pop.hiv_status
+    # Test probability of partnering with someone with HIV by sex and age group
+    # 5 age groups (15-25, 25-35, 35-45, 45-55, 55-65) and 2 sexes = 10 groups
+    N_group = N // 10  # number of people we will put in each group
+    sex_list = []
+    age_group_list = []
+    HIV_list = []
+    HIV_ratio = 10  # mark 1 in 10 people as HIV positive
+    for sex in SexType:
+        for age_group in range(5):
+            sex_list += [sex] * N_group
+            age_group_list += [age_group] * N_group
+            HIV_list += [True] * (N_group // HIV_ratio) + [False] * (N_group - N_group//HIV_ratio)
+    pop.data[col.SEX] = np.array(sex_list)
+    pop.data[col.SEX_MIX_AGE_GROUP] = np.array(age_group_list)
+    pop.data[col.HIV_STATUS] = np.array(HIV_list)
+    pop.data[col.NUM_PARTNERS] = 1  # give everyone a single stp to start with
+
+    # if everyone has the same number of partners,
+    # probability of being with someone with HIV should be = HIV prevalence
+    hiv_module.update_partner_risk_vectors(pop)
+    expectation = np.array([0.1]*5)
+    assert np.allclose(hiv_module.stp_HIV_rate[SexType.Male], expectation)
+    assert np.allclose(hiv_module.stp_HIV_rate[SexType.Female], expectation)
+
+    # Check for differences in male and female rate correctly
+    # change HIV rate in men to double
+    males = pop.data.index[pop.data[col.SEX] == SexType.Male]
+    # transform group fails when only grouped by one field
+    # appears to change the type of the object passed to the function!
+    male_HIV_status = pop.transform_group([col.SEX_MIX_AGE_GROUP, col.SEX], lambda x, y: np.array(
+        [True] * (2 * N_group // HIV_ratio) +
+        [False] * (N_group - 2*N_group // HIV_ratio)), False, males)
+    pop.data.loc[males, col.HIV_STATUS] = male_HIV_status
+    hiv_module.update_partner_risk_vectors(pop)
+    assert np.allclose(hiv_module.stp_HIV_rate[SexType.Male], 2*expectation)
+    assert np.allclose(hiv_module.stp_HIV_rate[SexType.Female], expectation)
+
+    # Check for difference when changing number of partners between HIV + / - people
+    HIV_positive = pop.data.index[pop.data[col.HIV_STATUS]]
+    # 2 partners for each HIV+ person, one for each HIV- person.
+    pop.data.loc[HIV_positive, col.NUM_PARTNERS] = 2
+    expectation_male = (2 * 0.2) / (2*0.2 + 0.8)
+    expectation_female = (2 * 0.1) / (2*0.1 + 0.9)
+    hiv_module.update_partner_risk_vectors(pop)
+    assert np.allclose(hiv_module.stp_HIV_rate[SexType.Male], expectation_male)
+    assert np.allclose(hiv_module.stp_HIV_rate[SexType.Female], expectation_female)
+
+
+def test_viral_group_risk_vector():
+    N = 10000
+    pop = Population(size=N, start_date=date(1989, 1, 1))
+    hiv_module = pop.hiv_status
+    # Test probability of partnering with someone with HIV by sex and age group
+    # 5 age groups (15-25, 25-35, 35-45, 45-55, 55-65) and 2 sexes = 10 groups
+    N_group = N // 10  # number of people we will put in each group
+    sex_list = []
+    age_group_list = []
+    HIV_list = []
+    HIV_ratio = 10  # mark 1 in 10 people as HIV positive
+    for sex in SexType:
+        for age_group in range(5):
+            sex_list += [sex] * N_group
+            age_group_list += [age_group] * N_group
+            HIV_list += [True] * (N_group // HIV_ratio) + [False] * (N_group - N_group//HIV_ratio)
+    pop.data[col.SEX] = np.array(sex_list)
+    pop.data[col.SEX_MIX_AGE_GROUP] = np.array(age_group_list)
+    pop.data[col.NUM_PARTNERS] = 1  # give everyone a single stp to start with]
+    pop.data[col.VIRAL_LOAD_GROUP] = 1  # put everyone in the same viral load group to begin with
+    hiv_module.update_partner_risk_vectors(pop)  # probability of group 1 should be 100%
+    expectation = np.array([0., 1., 0., 0., 0., 0., 0.])
+    assert np.allclose(hiv_module.stp_viral_group_rate[SexType.Male], expectation)
+    assert np.allclose(hiv_module.stp_viral_group_rate[SexType.Female], expectation)
+    pop.data[col.VIRAL_LOAD_GROUP] = np.array([1, 2] * (N // 2))  # alternate groups 1 & 2
+    pop.data.loc[pop.data[col.VIRAL_LOAD_GROUP] == 1, col.NUM_PARTNERS] = 2
+    hiv_module.update_partner_risk_vectors(pop)
+    expectation = np.array([0., 2/3, 1/3, 0., 0., 0., 0.])
+    assert np.allclose(hiv_module.stp_viral_group_rate[SexType.Male], expectation)
+    assert np.allclose(hiv_module.stp_viral_group_rate[SexType.Female], expectation)
+    # check for appropriate sex differences
+    pop.data.loc[(pop.data[col.VIRAL_LOAD_GROUP] == 1) & (
+        pop.data[col.SEX] == SexType.Female), col.VIRAL_LOAD_GROUP] = 3
+    hiv_module.update_partner_risk_vectors(pop)
+    expecation_female = np.array([0., 0., 1/3, 2/3, 0., 0., 0.])
+    assert np.allclose(hiv_module.stp_viral_group_rate[SexType.Male], expectation)
+    assert np.allclose(hiv_module.stp_viral_group_rate[SexType.Female], expecation_female)