Female genital tract host factors and tenofovir and lamivudine active metabolites.

BACKGROUND: We previously reported the effect of contraception on cervical tenofovir concentrations in Ugandan women living with HIV. Here we explored the role of cervicovaginal cytokines and drug metabolizing enzymes and transporters (DMETs) to elucidate FGT drug disposition in a Ugandan cohort. METHODS: Cervicovaginal fluid and cervical biopsies were collected from Ugandan women living with HIV receiving tenofovir/lamivudine-based therapy and intramuscular depot medroxyprogesterone acetate (DMPA-IM; n=25), copper IUD (cuIUD; n=12), or condoms (n=13) as contraception. Cytokines were measured in cervicovaginal fluid (CVF). Ectocervical tenofovir diphosphate (TFVdp) and lamivudine triphosphate (3TCtp), dATP/dCTP concentrations, and immune marker/DMETs gene expression were measured in cervical biopsies. RESULTS: Cervical 3TCtp was not correlated with any CVF cytokines. Cervical TFVdp was correlated with IL-10, IL-7, and IL-17 in CVF. CCR5 mRNA expression in cervical biopsies was higher in cuIUD-users versus condoms-users. Using multivariable linear regression, CVF IL-17, tissue dATP, plasma estradiol, and plasma tenofovir were all significant predictors of cervical TFVdp. Tissue dCTP and plasma lamivudine were significant predictors of cervical 3TCtp. CONCLUSIONS: TFVdp concentrations in cervix appear to be influenced by local inflammation. In contrast, 3TCtp FGT exposure was not affected by genital inflammation or DMETS. CuIUD users have more immune cells present, which may in turn influence local TFVdp disposition.

Increased difficulty accessing food and income change during the COVID-19 pandemic among youth living in the eThekwini district, South Africa.

OBJECTIVE: To estimate the effect of income change on difficulty accessing food since the COVID-19 pandemic for South African youth and evaluate whether this effect was modified by receiving social grants. DESIGN: A cross-sectional, online survey was conducted between December 2021 and May 2022. Primary outcome was increased difficulty accessing food since the COVID-19 pandemic. Income change was categorised as 'Decreased a lot', 'Decreased slightly' and 'Unchanged or increased'. Multivariable logistic regressions were used, with an interaction term between social grant receipt and income change. SETTING: eThekwini district, South Africa. PARTICIPANTS: Youth aged 16-24 years. RESULTS: Among 1,620 participants, median age was 22 years (IQR 19-24); 861 (53 %) were women; 476 (29 %) reported increased difficulty accessing food; 297 (18 %) reported that income decreased a lot, of whom 149 (50 %) did not receive social grants. Experiencing a large income decrease was highly associated with increased difficulty accessing food during the COVID-19 pandemic (adjusted OR [aOR] 3·63, 95 % CI 2·70, 4·88). The aOR for the effect of a large income decrease on difficulty accessing food, compared to no income change, were 1·49 (95 % CI 0·98, 2·28) among participants receiving social grants, and 6·63 (95 % CI 4·39, 9·99) among participants not receiving social grants. CONCLUSIONS: While social grant support made a great difference in lowering the effect of income decrease on difficulty accessing food, it was insufficient to fully protect youth from those difficulties. In post-pandemic recovery efforts, there is a critical need to support youth through economic empowerment programming and food schemes.

'Life became harder with COVID-19': exploring the experiences of the COVID-19 pandemic among youth living in eThekwini district, South Africa.

BACKGROUND: In South Africa, pervasive age and gender inequities have been exacerbated by the COVID-19 pandemic and public health response. We aimed to explore experiences of the COVID-19 pandemic among youth in eThekwini district, South Africa. METHODS: Between December 2021-May 2022 we explored experiences of the COVID-19 pandemic on youth aged 16-24 residing in eThekwini, South Africa. We collated responses to the open-ended question "Has the COVID-19 pandemic affected you in any other way you want to tell us about?" in an online survey focused on understanding the pandemic's multi-levelled health and social effects. We used a thematic analysis to summarise the responses. RESULTS: Of 2,068 respondents, 256 (12.4%, median age = 22, 60.9% women) completed the open-ended survey question (11% in isiZulu). Results were organized into three main themes encompassing (1) COVID-19-related loss, fear, grief, and exacerbated mental and physical health concerns; (2) COVID-19-related intensified hardships, which contributed to financial, employment, food, education, and relationship insecurities for individuals and households; and (3) positive effects of the pandemic response, including the benefits of government policies and silver linings to government restrictions. CONCLUSIONS: We found that South African youth experienced significant grief and multiple losses (e.g., death, income, job, and educational) during the COVID-19 pandemic. Trauma-aware interventions that provide economic and educational opportunities must be included in post-COVID recovery efforts.

Effects of injectable contraception with depot medroxyprogesterone acetate or norethisterone enanthate on estradiol levels and menstrual, psychological and behavioral measures relevant to HIV risk: The WHICH randomized trial.

BACKGROUND: Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels. METHODS: This open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18-40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W). RESULTS: At 25W, median 17ß estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured. CONCLUSIONS: Estradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question. TRIAL REGISTRATION: PACTR 202009758229976.

Economic hardship and perpetration of intimate partner violence by young men in South Africa during the COVID-19 pandemic (2021-2022): a cross-sectional study.

BACKGROUND: Economic hardship is a potential trigger for intimate partner violence (IPV) perpetration. While higher IPV rates have been reported in low-income regions, few African studies have focused on IPV being triggered by economic hardship among young men during the COVID-19 pandemic. We therefore estimated economic hardship's effect on IPV perpetration by young men in eThekwini District, South Africa, during the COVID-19 pandemic. METHODS: A cross-sectional survey of COVID-19 pandemic experiences was conducted among youth aged 16-24 years through an anonymous self-administered questionnaire, including questions about economic hardship (increased difficulty accessing food or decreased income) and IPV perpetration. A prespecified statistical analysis plan with a directed acyclic graph of assumed exposure, outcome, and confounder relationships guided our analyses. We measured association of economic hardship and IPV perpetration through odds ratios (ORs) computed from a multivariable logistic regressions adjusted for measured confounders. Secondary outcomes of physical and sexual IPV perpetration were analyzed separately using the same specifications. Propensity score matching weights (PS-MW) were used in sensitivity analyses. Analysis code repository: https://github.com/CAndrewBasham/Economic_Hardship_IPV_perpetration/ RESULTS: Among 592 participants, 12.5% reported perpetrating IPV, 67.6% of whom reported economic hardship, compared with 45.6% of those not reporting IPV perpetration (crude OR = 2.49). Median age was 22 years (interquartile range 20-24). Most (80%) were in a relationship and living together. Three quarters identified as Black, 92.1% were heterosexual, and half had monthly household income < R1600. We estimated an effect of economic hardship on the odds of perpetrating IPV as OR = 1.83 (CI 0.98-3.47) for IPV perpetration overall, OR = 6.99 (CI 1.85-36.59) for sexual IPV perpetration, and OR = 1.34 (CI 0.69-2.63) for physical IPV perpetration. PS-MW-weighted ORs for IPV perpetration by economic hardship were 1.57 (overall), 4.45 (sexual), and 1.26 (physical). CONCLUSION: We estimated 83% higher odds of self-reported IPV perpetration by self-reported economic hardship among young South African men during the COVID-19 pandemic. The odds of sexual IPV perpetration were The seven-times higher by economic hardship, although with limited precision. Among young men in South Africa, economic hardship during COVID-19 was associated with IPV perpetration by men. Our findings warrant culturally relevant and youth-oriented interventions among young men to reduce the likelihood of IPV perpetration should they experience economic hardship. Further research into possible causal mechanisms between economic hardship and IPV perpetration could inform public health measures in future pandemic emergencies.

Impact of the COVID-19 pandemic on women's contraceptive use: a mixed-methods study in South Africa and Zambia.

Background: The COVID-19 pandemic affected global access to health services, including contraception. We sought to explore effects of the pandemic on family planning (FP) service provision and use in South Africa and Zambia, including on implant and intrauterine device (IUD) users' desire and ability to obtain removal. Methods: Between August 2020 and April 2021, we conducted surveys with 537 women participating in an ongoing longitudinal contraceptive continuation study. We also carried out in-depth interviews with 39 of the survey participants and 36 key informants involved in FP provision. We conducted descriptive analysis of survey responses and thematic analysis of interviews. Results: Contraceptive use changed minimally in this sample with the emergence of COVID-19. Fewer than half of women (n=220) reported attempting to access FP since the start of the pandemic, the vast majority of whom were using short-acting methods. Among those who sought services, 95% obtained their preferred method. The proportion of women not using a method before and after pandemic start did not change in Zambia (31%); in South Africa, the proportion increased from 8% to 10%. Less than 7% of implant or IUD users in either country reported wanting removal. Among those who sought removal (n=22), 91% (n=10) in Zambia and 55% (n=6) in South Africa successfully obtained removal. In qualitative interviews, women with challenges accessing FP services mentioned long queues, deprioritization of contraceptive services, lack of transportation, stock-outs, and fear of contracting COVID-19 at a facility. Key informants reported stock-outs, especially of injectables, and staff shortages as barriers. Conclusions: We did not find a substantial impact of COVID-19 on contraceptive access among this sample; however, providers and others involved in service provision identified risks to continuity of care. As the COVID-19 pandemic wanes, it continues to be important to monitor people's ability to access their preferred contraceptive methods.

Misreporting contraceptive use and the association of peak study progestin levels with weight and BMI among women randomized to the progestin-only injectable contraceptives DMPA-IM and NET-EN.

Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan Africa. Insufficient robust data on their relative side-effects and serum concentrations limit understanding of reported outcomes in contraception trials. The WHICH clinical trial randomized HIV-negative women to DMPA-IM (n = 262) or norethisterone enanthate (NET-EN) (n = 259) at two South African sites between 2018-2019. We measured serum concentrations of study and non-study progestins at initiation (D0) and peak serum levels, one week after the 24-week injection [25 weeks (25W)], (n = 435) and investigated associations between study progestin levels, and BMI and weight of participants. Peak median serum concentrations were 6.59 (IQR 4.80; 8.70) nM for medroxyprogesterone (MPA) (n = 161) and 13.6 (IQR 9.01; 19.0) nM for norethisterone (NET) (n = 155). MPA was the most commonly quantifiable non-study progestin at D0 in both arms (54%) and at 25W in the NET-EN arm (27%), followed by NET at D0 in both arms (29%) and at 25W in the DMPA-IM arm (19%). Levonorgestrel was quantifiable in both arms [D0 (6.9%); 25W (3.4%)], while other progestins were quantifiable in ≤ 14 participants. Significant negative time-varying associations were detected between MPA and NET concentrations and weight and BMI in both contraceptive arms and a significant increase was detected for peak serum progestin concentrations for normal weight versus obese women. Contraceptive-related reported outcomes are likely confounded by MPA, more so than NET, with reported DMPA-IM effects likely underestimated, at sites where DMPA-IM is widely used, due to misreporting of contraceptive use before and during trials, and 'tail' effects of DMPA-IM use more than six months before trial enrolment. Peak serum levels of MPA and NET are negatively associated with BMI and weight, suggesting another source of variability between trial outcomes and a potential increase in side-effects for normal weight versus overweight and obese women. Trail registration: The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).