Punishment resistance for cocaine is associated with inflexible habits in rats.

Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration. We then exposed them to four days of punishment testing in which footshock was delivered randomly on one-third of trials. Before and after punishment testing (four days pre-punishment and ≥ four days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance for cocaine was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment in males, although it was associated with habitual responding both pre- and post-punishment in females, indicating that punishment resistance was predicted by habitual responding in food-seeking females. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.

Punishment resistance for cocaine is associated with inflexible habits in rats.

Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration (2 h/day). We then exposed them to 4 days of punishment testing, in which footshock (0.4 mA, 0.3 s) was delivered randomly on one-third of trials, immediately following completion of seeking and prior to extension of the taking lever. Before and after punishment testing (4 days pre-punishment and ≥4 days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.

Modeling the potential impact of pre-exposure prophylaxis for HIV among men who have sex with men in Cameroon.

BACKGROUND: Men who have sex with men (MSM) are consistently burdened by HIV at higher levels than other adults. While HIV prevention programs for MSM are growing in coverage and quality, HIV incidence remains high. In response, pre-exposure prophylaxis (PrEP) was introduced in 2019 to support HIV risk reduction among MSM in Cameroon. Understanding how PrEP initiation programs will change the HIV prevalence among MSM in Cameroon is important to developing effective programs. METHODS: This study uses a mathematical model to simulate population-level HIV transmission among MSM in the cities of Yaoundé and Douala, Cameroon. PrEP is incorporated into the model at rates that equal 25%, 50%, or 75% coverage after twenty years to assess the potential effects on HIV prevalence among MSM, requiring annual initiation rates of 2.5%, 6.8%, and 17.2% for Yaoundé and 2.2%, 5.6%, and 13.4% for Douala, respectively. The data utilized for this model are from a cross sectional study which recruited MSM through respondent-driven sampling of MSM in two major cities in Cameroon: Yaoundé and Douala. RESULTS: The model estimated an HIV prevalence of 43.2% among MSM, annual HIV diagnoses of 300 per 10,000 MSM and antiretroviral therapy (ART) coverage of 53.9% in Yaoundé. In Douala, estimated prevalence is 26.5% among MSM, 167 per 10,000 MSM annual diagnoses and ART coverage of 72.0%. Standalone PrEP interventions aimed at 50% coverage at the end of a 20-year program would reduce the prevalence from 43.2% to 35.4% in Yaoundé and from 26.5 to 20.1% in Douala. Combining PrEP with a 10% increase in HIV testing would decrease the number of MSM living with HIV and unaware of their status from 9.8 to 6.0% in Yaoundé and from 8.7 to 4.6% in Douala. CONCLUSIONS: PrEP would be beneficial in reducing prevalence even at varying initiation and coverage levels. Combination of PrEP and increased HIV testing further decreased the number of undiagnosed MSM. This study supports the utility of implementing PrEP as part of comprehensive HIV prevention programming among MSM in Cameroon.

HIV Pre-exposure Prophylaxis Uptake and Continuation Among Key Populations in Cameroon: Lessons Learned From the CHAMP Program.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is proven to be a highly effective HIV prevention method for key populations. However, its scale-up in resource-limited settings remains suboptimal. This paper seeks to describe PrEP initiation and continuation among key populations in Cameroon. METHODOLOGY: From June 2019 through October 2020, we collected routine program data on PrEP uptake and continuation among female sex workers (FSWs) and men who have sex with men (MSM) in the Continuum of prevention, care and treatment of HIV/AIDS with Most-at-risk Populations (CHAMP) program in Cameroon. PrEP was offered to clients who tested negative for HIV and were assessed to potentially benefit from PrEP. Using survival analysis, we identified factors associated with PrEP discontinuation over time with significance set at 5%. RESULTS: Overall, 27,750 clients were sensitized for PrEP of whom 3,138 persons were eligible to start PrEP and 1,409 (45%; FSW: 691 and MSM: 718) initiated PrEP. The PrEP continuation rate was 37% at 3 months, 28% at 6 months and 19% at 12 months. PrEP discontinuation was significantly higher among FSW than MSM [adjusted hazard ratio (aHR) 1.5 (95% CI: 1.2 to 1.9)] in Yaounde [aHR 1.5 (95% CI: 1.2 to 1.9)] and Bafoussam/Bertoua [aHR 3.1 (2.2-4.5)] relative to Douala. Discontinuation was lower among those with moderate [aHR 0.3 (0.3-0.4)] or good adherence [aHR 0.4 (0.3-0.6)] compared with poor adherence (all P < 0.001). CONCLUSION: Differentiated approaches to deliver PrEP, create demand, and provide more intensive support for adherence and continuation may support scale-up of PrEP in Cameroon for equitable and prolonged impact on HIV prevention.

Unmet Need for Family Planning and Experience of Unintended Pregnancy Among Female Sex Workers in Urban Cameroon: Results From a National Cross-Sectional Study.

BACKGROUND: Female sex workers (FSWs) in Cameroon commonly have unmet need for contraception posing a high risk of unintended pregnancy. Unintended pregnancy leads to a range of outcomes, and due to legal restrictions, FSWs often seek unsafe abortions. Aside from the high burden of HIV, little is known about the broader sexual and reproductive health of FSWs in Cameroon. METHODS: From December 2015 to October 2016, we recruited FSWs aged ≥18 years through respondent-driven sampling across 5 Cameroonian cities. Cross-sectional data were collected through a behavioral questionnaire. Modified-robust Poisson regression was used to approximate adjusted prevalence ratios (aPR) for TOP and current use of effective nonbarrier contraception. RESULTS: Among 2,255 FSWs (median age 28 years), 57.6% reported history of unintended pregnancy and 40.0% reported prior TOP. In multivariable analysis, TOP history was associated with current nonbarrier contraceptive use (aPR=1.23, 95% confidence interval [CI]=1.07, 1.42); ever using emergency contraception (aPR=1.34, 95% CI=1.17, 1.55); >60 clients in the past month (aPR=1.29, 95% CI= 1.07, 1.54) compared to ≤30; inconsistent condom use with clients (aPR=1.17, 95% CI=1.00, 1.37); ever experiencing physical violence (aPR=1.24, 95% CI=1.09, 1.42); and older age. Most (76.5%) women used male condoms for contraception, but only 33.2% reported consistent condom use with all partners. Overall, 26.4% of women reported currently using a nonbarrier contraceptive method, and 6.2% reported using a long-acting method. Previous TOP (aPR=1.41, 95%CI=1.16, 1.72) and ever using emergency contraception (aPR=2.70, 95% CI=2.23, 3.26) were associated with higher nonbarrier contraceptive use. Recent receipt of HIV information (aPR=0.72, 95% CI=0.59, 0.89) and membership in an FSW community-based organization (aPR=0.73, 95% CI=0.57, 0.92) were associated with lower use nonbarrier contraceptive use. CONCLUSIONS: Experience of unintended pregnancies and TOP is common among FSWs in Cameroon. Given the low use of nonbarrier contraceptive methods and inconsistent condom use, FSWs are at risk of repeat unintended pregnancies. Improved integration of client-centered, voluntary family planning within community-led HIV services may better support the sexual and reproductive health and human rights of FSWs consistent with the United Nations Declaration of Human Rights.