STI prevalence, partner notification and HIV risk perception in a cohort of women completing STI screening as part of a safer conception study.

BACKGROUND: Integrating STI and pre-exposure prophylaxis (PrEP) care may optimize sexual and reproductive health. METHODS: We nested an STI-sub-study within an HIV prevention cohort (Parent study) of 18-35-year-old women from South Africa, planning pregnancy with a partner with HIV or of unknown-serostatus. Parent-study women completed annual surveys regarding HIV-risk perceptions and were offered oral PrEP. PrEP initiators completed quarterly plasma tenofovir testing. Sub-study women completed STI screening at enrollment, 6 months, onset of pregnancy, and in the third trimester via examination, vaginal swabs tested via PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and blood tested for Treponema pallidum. Follow-up was six months. Women with STIs were treated, offered partner notification (PN) cards, and surveyed regarding PN practices. We describe STI prevalence and incidence, and model factors associated with prevalent infection. STI sub-study and Parent-study-only participants were matched on age and number of days on study to assess HIV-risk perception scores between the two groups and the proportion with detectable tenofovir. RESULTS: Among 50 sub-study participants, 15 (30%) had prevalent STI. All 13 completing follow-up reported PN. Most did not prefer assisted PN. Mean HIV risk perception scores and proportion with detected plasma TFV were similar across groups. CONCLUSIONS: High STI prevalence supports the importance of laboratory screening to optimize sexual health for women planning pregnancy. Rates of self-reported PN are reassuring; low interest in assisted PN suggests the need for alternative approaches. Enhanced STI care did not affect HIV-risk perception or PrEP adherence, however both were relatively high in this cohort.

Teclistamab: Mechanism of action, clinical, and translational science.

Multiple myeloma (MM) remains incurable despite improvements in treatment options. B-cell maturation antigen (BCMA) is predominantly expressed in B-lineage cells and represents a promising new target for MM. Teclistamab (TECVAYLITM ) is the first T-cell redirecting bispecific antibody approved for patients with MM. Targeting both CD3 receptor complex on T cells and BCMA on myeloma cells, teclistamab leads to T-cell activation and subsequent lysis of BCMA+ cells. The recommended dose of teclistamab is 1.5 mg/kg subcutaneous weekly after two step-up doses of 0.06 and 0.3 mg/kg, which was selected after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data. Exposure-response analyses of efficacy and safety data were also used to confirm the teclistamab dose. Teclistamab resulted in a high rate of deep and durable responses (63% overall response, 45.5% complete response or better, with 22 months median duration of response) in patients with triple-exposed relapsed/refractory MM. Common adverse reactions included cytokine release syndrome, hematologic abnormalities, and infections. Teclistamab is currently being investigated as monotherapy as well as combination therapy across different MM indications.

Comparative Effectiveness of Teclistamab Versus Real-World Physician's Choice of Therapy in LocoMMotion and MoMMent in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma.

INTRODUCTION: Teclistamab is the first approved B cell maturation antigen × CD3 bispecific antibody with precision dosing for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). We compared the effectiveness of teclistamab in MajesTEC-1 versus real-world physician's choice of therapy (RWPC) in patients from the prospective, non-interventional LocoMMotion and MoMMent studies. METHODS: Patients treated with teclistamab from MajesTEC-1 (N = 165) were compared with an external control arm from LocoMMotion (N = 248) or LocoMMotion + MoMMent pooled (N = 302). Inverse probability of treatment weighting adjusted for imbalances in prognostic baseline characteristics. The relative effect of teclistamab versus RWPC for overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate was estimated with an odds ratio using weighted logistic regression transformed into a response-rate ratio (RR) and 95% confidence interval (CI). Weighted proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Baseline characteristics were well balanced between treatment cohorts after reweighting. Patients treated with teclistamab had significantly improved outcomes versus RWPC in LocoMMotion: ORR (RR [95% CI], 2.44 [1.79-3.33]; p < 0.0001), ≥ VGPR (RR 5.78 [3.74-8.93]; p < 0.0001), ≥ CR (RR 113.73 [15.68-825.13]; p < 0.0001), DOR (HR 0.39 [0.24-0.64]; p = 0.0002), PFS (HR 0.48 [0.35-0.64]; p < 0.0001), and OS (HR 0.64 [0.46-0.88]; p = 0.0055). Teclistamab versus RWPC in LocoMMotion + MoMMent also had significantly improved outcomes: ORR (RR 2.41 [1.80-3.23]; p < 0.0001), ≥ VGPR (RR 5.91 [3.93-8.88]; p < 0.0001), ≥ CR (RR 132.32 [19.06-918.47]; p < 0.0001), DOR (HR 0.43 [0.26-0.71]; p = 0.0011), PFS (HR 0.49 [0.37-0.66]; p < 0.0001), and OS (HR 0.69 [0.50-0.95]; p = 0.0247). CONCLUSION: Teclistamab demonstrated significantly improved effectiveness over RWPC in LocoMMotion ± MoMMent, emphasizing its clinical benefit as a highly effective treatment for patients with TCE RRMM. TRIAL REGISTRATION: MajesTEC-1, ClinicalTrials.gov NCT03145181 (phase 1) and NCT04557098 (phase 2); LocoMMotion, ClinicalTrials.gov NCT04035226; MoMMent, ClinicalTrials.gov NCT05160584.

Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptives.

BACKGROUND: South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. METHODS: We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18-33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. RESULTS: There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups- 18-21 years (46%), 22-25 years (42%) and 26-33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18-21 years) more likely to acquire CT (75.9/100 wy) compared to 26-33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26-33 year old group (82.7/100 wy) compared to the 18-21 year olds (8.4/100 wy; p = 0.01). CONCLUSIONS: Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.

Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women.

Background: Daily, oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) reduces HIV acquisition for African women. Adherence is key to efficacy and patterns of adherence can be highly variable in real-world settings. Using group-based trajectory modeling (GBTM), we sought to identify distinct patterns of periconception PrEP adherence and evaluate potential baseline predictors of such adherence trajectories. Methods: We conducted a single-arm longitudinal study for women aged 18-35 years living in Durban, South Africa with personal or partner plans for pregnancy with a partner with HIV or of unknown serostatus. Participants were offered safer conception counseling, including daily oral PrEP; women who initiated PrEP were given a bottle with an electronic pillcap that recorded when device opens. Weekly adherence to daily PrEP was modeled using GBTM with a censored normal outcome distribution as a function of weeks since PrEP initiation. The number and functional form of the adherence trajectory groups were primarily selected based on Bayesian information criteria (BIC) and confirmed by mean estimated probabilities of group membership. A multivariable version of the selected model assessed baseline predictors of membership in adherence trajectory groups. Results: Overall mean (95% CI) adherence to PrEP was 63% (60%, 67%). We identified four groups of women with distinct patterns of adherence: (1) high (i.e., ≥6 doses per week) steady adherence throughout follow-up (22% of PrEP initiators); (2) moderate (i.e., 4-5 doses per week), but steady adherence (31%); (3) initially high, but consistently declining adherence (21%); and (4) initially moderate adherence, followed by a rapid decline and subsequent rebound (26%). In multivariable-adjusted analyses, older age was associated with membership in the high, steady adherence group as compared to the group identified with an adherence trajectory of initially high, then decline, and finally a rebound. Conclusions: GBTM is useful for exploring potential heterogeneity in longitudinal patterns of medication adherence. Although a large proportion of women in this study achieved high levels of adherence by electronic pillcap initially, far fewer women maintained these levels consistently. Knowledge of different adherence trajectories could be used to develop targeted strategies for optimizing HIV prevention during periconception.

A continuum of individual-level factors that influence modern contraceptive uptake and use: perspectives from community members and healthcare providers in Durban, South Africa.

BACKGROUND: South Africa faces numerous sexual and reproductive health challenges that can be mitigated with contraceptive use. Contraceptive use is defined and measured as use, non-use, or discontinued use. Research has shown that there are expanded definitions of use beyond these categories. Identifying such categories may assist in a better understanding of factors that influence contraceptive use. SETTING AND METHODOLOGY: This qualitative study was conducted in the eThekwini Municipality in KwaZulu-Natal, South Africa. The aim was to explore the factors influencing the uptake and use of modern contraception. One hundred and twenty-seven participants were enrolled in this study. One hundred and three of those were community members, and twenty-five were healthcare providers. Focus group discussions and in-depth interviews were conducted to gather the data. Data analysis was facilitated using NVivo 10 software. RESULTS: The data show that numerous factors influence contraceptive uptake and use. From these factors, a continuum of use that captures a variety of states of use emerged. Five different states of use were uncovered: no-use, vulnerable use, compelled use, conditional use, and autonomous use. The development of the model illustrates the complexity of contraceptive needs and that it extends beyond definitions found in policies and large-scale surveys. Expanding conceptions of use can aid in developing counselling and information support tools that can improve the uptake and continued use of modern contraception.

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa.

We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants ever tested for Hepatitis C.

Teclistamab versus real-world physician's choice of therapy in triple-class exposed relapsed/refractory multiple myeloma.

Aim: We compared the effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC) in triple-class exposed relapsed/refractory multiple myeloma. Materials & methods: MajesTEC-1 eligibility criteria were applied to the RWPC cohort. Baseline covariate imbalances were adjusted using inverse probability of treatment weighting. Overall survival, progression-free survival and time to next treatment were compared. Results: After inverse probability of treatment weighting, baseline characteristics were similar between cohorts (teclistamab, n = 165; RWPC, n = 364 [766 observations]). Teclistamab treated patients had numerically better overall survival (hazard ratio [HR]: 0.82 [95% CI: 0.59-1.14]; p = 0.233) and significantly greater progression-free survival (HR: 0.43 [0.33-0.56]; p < 0.0001) and time to next treatment (HR: 0.36 [0.27-0.49]; p < 0.0001) versus the RWPC cohort. Conclusion: Teclistamab offered clinical benefit over RWPC in triple-class exposed relapsed/refractory multiple myeloma.

Perspectives on sexual and reproductive health self-care among women, healthcare providers, and other key informants: a mixed-methods study in South Africa and Zambia.

BACKGROUND: "Self-care" for sexual and reproductive health (SRH) includes contraceptive methods and other supplies that people can use with or without the support of a healthcare provider. Self-administered tests, self-injection of injectable contraception, or self-removal of intrauterine devices (IUDs) can increase people's access to and autonomy over their own SRH. Objectives of this study were to assess women's current interest in and use of SRH self-care and explore key informants' (KI) opinions of self-care, especially during the COVID-19 pandemic. METHODS: Data for this study came from female participants in the longitudinal Contraceptive Use Beyond ECHO (CUBE) study, and KIs, including healthcare providers, in South Africa and Zambia between September 2020 and June 2021. For this analysis, we used data from a participant phone survey (n = 537), and from in-depth interviews (IDIs) completed with a sub-sample of women (n = 39) and KIs (n = 36). Survey data were analyzed with descriptive statistics, and IDI data were analyzed using applied thematic analysis. RESULTS: Female survey participants in South Africa were more interested in learning about emergency contraceptive pills, subcutaneous injectable contraception, and CycleBeads, while Zambian participants wanted more information and access to condoms. However, in IDIs in both countries, women described minimal experience with self-care beyond condom use. In the Zambian KI IDIs, COVID-19 led to increased self-care counseling on subcutaneous injectable contraception and HIV self-testing. KIs who do not counsel on self-care were concerned that women may harm themselves or blame the provider for difficulties. Two KIs thought that women could possibly self-remove IUDs, but most expressed concerns. Reported barriers to self-care included COVID movement restrictions, transport costs, lack of accessible pharmacies, women's low awareness, and possible stigma. CONCLUSIONS: Women surveyed reported interest in learning more about SRH self-care methods and resources, but in IDIs did not report extensive previous use besides condoms. KIs described some concerns about women's ability to use self-care methods. Counseling on and provision of self-care methods and supplies may have increased during the COVID-19 pandemic, but ensuring that self-care is more than just a temporary measure in health systems has the potential to increase access to SRH care and support women's autonomy and healthcare needs.

BACKGROUND: "Self-care" refers to healthcare that does not have to be given by a provider, but that people can use themselves. In sexual and reproductive health (SRH), this includes medicines or supplies like pills and injections that people can use to prevent or test for pregnancy or sexually transmitted infections. This study wanted to better understand women's interest in and use of SRH self-care and explore key informants' opinions of self-care, especially during the COVID-19 pandemic. METHODS: We surveyed 537 women in KwaZulu-Natal province, South Africa and Lusaka, Zambia in 2020­2021. We also conducted interviews with 39 women and 36 key informants, including healthcare providers, government officials, and community advocates. RESULTS: Women surveyed in South Africa were more interested than those in Zambia in learning more about self-care contraception, especially daily pills, emergency pills, and injections they could give themselves. In interviews, some key informants said that they do not tell women about self-care because they worried that women could hurt themselves or blame the provider if they experienced problems. COVID movement restrictions, transport costs, and inaccessible pharmacies were all barriers that key informants mentioned to accessing tests, tools, or contraceptive methods that women could give or use themselves. CONCLUSIONS: Women surveyed were interested in learning more about self-care and those interviewed reported minimal previous use of self-care methods besides condoms. Providers also have some concerns about women's ability to use self-care methods. Counseling on and providing self-care methods and supplies may have increased during COVID-19, but increasing access to self-care could help more women take care of their own sexual and reproductive healthcare.

"I am scared, I do not want to lie": exploring the impacts of COVID-19 on engagement in care, perceived health, relationship dynamics, and parenting among postpartum women with HIV in South Africa.

BACKGROUND: COVID-19 and efforts to manage widespread infection may compromise HIV care engagement. The COVID-19-related factors linked to reduced HIV engagement have not been assessed among postpartum women with HIV, who are at heightened risk of attrition under non-pandemic circumstances. To mitigate the effects of the pandemic on care engagement and to prepare for future public health crises, it is critical to understand how COVID-19 has impacted (1) engagement in care and (2) factors that may act as barriers to care engagement. METHODS: A quantitative assessment of COVID-19-related experiences was added to a longitudinal cohort study assessing predictors of postpartum attrition from HIV care among women in South Africa. Participants (N = 266) completed the assessment at 6, 12, 18, or 24 months postpartum between June and November of 2020. Those who endorsed one or more challenge related to engagement in care (making or keeping HIV care appointments, procuring HIV medications, procuring contraception, and/or accessing immunization services for infants; n = 55) were invited to complete a brief qualitative interview, which explored the specific factors driving these challenges, as well as other impacts of COVID-19 on care engagement. Within this subset, 53 participants completed an interview; qualitative data were analyzed via rapid analysis. RESULTS: Participants described key challenges that reduced their engagement in HIV care and identified four other domains of COVID-19-related impacts: physical health, mental health, relationship with a partner or with the father of the baby, and motherhood/caring for the new baby. Within these domains, specific themes and subthemes emerged, with some positive impacts of COVID-19 also reported (e.g., increased quality time, improved communication with partner, HIV disclosure). Coping strategies for COVID-19-related challenges (e.g., acceptance, spirituality, distraction) were also discussed. CONCLUSIONS: About one in five participants reported challenges accessing HIV care, medications, or services, and they faced complex, multilayered barriers to remaining engaged. Physical health, mental health, relationships with partners, and ability to care for their infant were also affected. Given the dynamic nature of the pandemic and general uncertainty about its course, ongoing assessment of pandemic-related challenges among postpartum women is needed to avoid HIV care disruptions and to support wellbeing.

Access to public sector family planning services and modern contraceptive methods in South Africa: A qualitative evaluation from community and health care provider perspectives.

Progress has been made to improve access to family planning services and contraceptive methods, yet many women still struggle to access contraception, increasing their risk for unintended pregnancy. This is also true for South Africa, where over fifty per cent of pregnancies are reported as unintended, even though contraception is freely available. There is also stagnation in the fertility rate indicators and contraceptive use data, indicating that there may be challenges to accessing contraception. This paper explores the evaluation of access to contraception from community and health care provider perspectives. This qualitative study explored factors affecting the uptake and use of contraception through focus group discussions (n = 14), in-depth interviews (n = 8), and drawings. Participants included male and female community members (n = 103) between 15 and 49 years of age, health care providers (n = 16), and key stakeholder informants (n = 8), with a total number of 127 participants. Thematic content analysis was used to explore the data using NVivo 10. Emergent themes were elucidated and thematically categorised. The results were categorised according to a priori access components. Overall, the results showed that the greatest obstacle to accessing contraception was the accommodation component. This included the effects of integrated care, long waiting times, and limited operational hours-all of which contributed to the discontinuation of contraception. Community members reported being satisfied with the accessibility and affordability components but less satisfied with the availability of trained providers and a variety of contraceptive methods. The accessibility and affordability themes also revealed the important role that individual agency and choice in service provider plays in accessing contraception. Data from the illustrations showed that adolescent males experienced the most geographic barriers. This study illustrated the importance of examining access as a holistic concept and to assess each component's influence on contraceptive uptake and use.

Comparative Efficacy of Teclistamab Versus Physician's Choice of Therapy in the Long-term Follow-up of APOLLO, POLLUX, CASTOR, and EQUULEUS Clinical Trials in Patients With Triple-class Exposed Relapsed or Refractory Multiple Myeloma.

BACKGROUND: The efficacy and safety of teclistamab in patients with RRMM who received ≥3 prior lines of therapy and were triple-class exposed (TCE) are being evaluated in the single-arm, multicohort, phase I/II MajesTEC-1 trial (NCT04557098). We evaluated the comparative effectiveness of teclistamab versus physician's choice (PC) of therapy in TCE RRMM patients. METHODS: Individual patient-level data from MajesTEC-1 patients who received teclistamab (1.5 mg/kg weekly; clinical cutoff March 16, 2022) were included. An external control arm was created from patients in long-term follow-up of 4 clinical trials of daratumumab who were treated with PC therapy after discontinuation of trial treatments. In the primary analysis, inverse probability of treatment weighting was used to adjust for imbalances in 9 baseline covariates. A fully adjusted model included 5 additional prognostic factors. Outcomes included overall response rate (ORR), very good partial response or better (≥VGPR) rate, overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT). RESULTS: After adjustment, baseline characteristics were balanced between cohorts. In the primary analysis, outcomes were significantly improved with teclistamab versus PC: ORR (OR [95% CI] 4.81 [3.04-7.72]; P < .0001); ≥VGPR rate (OR, 12.07 [6.91-22.11]; P < .0001); OS (HR, 0.54 [0.40-0.73]; P < .0001); PFS (HR, 0.59 [0.46-0.78]; P = .0001); and TTNT (HR, 0.32 [0.24-0.42]; P < .0001). Results of the fully adjusted model were consistent with the primary analysis. CONCLUSION: Teclistamab showed significantly improved effectiveness versus PC on all outcomes, highlighting its clinical benefit in patients with TCE RRMM and limited treatment options.

Detailed overview of incidence and management of cytokine release syndrome observed with teclistamab in the MajesTEC-1 study of patients with relapsed/refractory multiple myeloma.

BACKGROUND: Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma in the phase 1/2 MajesTEC-1 study. Cytokine release syndrome (CRS), a known manifestation of T-cell redirection, was observed in 119 of 165 patients (72.1%). METHODS: Patients received once-weekly teclistamab 1.5 mg/kg subcutaneously after two step-up doses (0.06 and 0.3 mg/kg). CRS was graded according to American Society for Transplantation and Cellular Therapy criteria and managed according to the study protocol, including use of tocilizumab and/or steroids. RESULTS: Most cases of CRS occurred during the step-up dosing schedule of teclistamab and were grade 1 (50.3% of patients) or grade 2 (21.2% of patients); a single case of grade 3 CRS was reported in a patient with concurrent grade 3 pneumonia. All CRS cases resolved and none led to treatment discontinuation. Overall, 33.3% of patients had >1 CRS event; CRS recurrence was reduced when tocilizumab was administered for the first CRS event compared with when it was not (20.0% vs. 62.2%, respectively). Baseline characteristics such as tumor burden and cytokine levels did not appear to predict CRS incidence or severity. CONCLUSIONS: Findings of this study support the need for preemptive planning and prompt management of CRS in patients treated with T-cell-engaging bispecific antibodies. Intervention with tocilizumab for CRS appears to decrease the likelihood of patients experiencing subsequent CRS events without compromising response to teclistamab. PLAIN LANGUAGE SUMMARY: Cytokine release syndrome (CRS), observed in 72.1% of patients treated with teclistamab in the MajesTEC-1 study, was mostly grade 1 or 2 and manageable, without requiring treatment discontinuation. Most CRS occurred during the step-up schedule, requiring vigilance during treatment initiation. Ensure fever is resolved and patients have no signs of infection before initiating the teclistamab step-up schedule or administering the next teclistamab dose, to avoid exacerbating CRS. Tocilizumab reduced the risk of subsequent CRS in patients receiving it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to teclistamab. No baseline characteristics, including tumor burden or cytokine levels, appeared to clearly predict for CRS occurrence or severity.

Comparative Efficacy of Teclistamab Versus Current Treatments in Real-World Clinical Practice in the Prospective LocoMMotion Study in Patients with Triple-Class-Exposed Relapsed and/or Refractory Multiple Myeloma.

INTRODUCTION: Patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE-RRMM) have a poor prognosis and limited treatment options. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, was studied in patients with TCE-RRMM in the single-arm MajesTEC-1 study. To assess the relative effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC), adjusted comparisons were performed using individual patient data from MajesTEC-1 and LocoMMotion, a prospective study of patients with TCE-RRMM. METHODS: An external control arm for MajesTEC-1 was created from patients in LocoMMotion (n = 248; clinical cut-off: November 2, 2021) and compared with treated patients (n = 165) from MajesTEC-1 (teclistamab 1.5 mg/kg weekly; clinical cut-off: March 16, 2022). Inverse probability weighting was used to adjust for imbalances in baseline covariates. For binary endpoints [overall response rate (ORR), very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR)], relative effect of teclistamab versus RWPC was estimated with an odds ratio and relative response rate and 95% confidence interval (CI), derived from weighted logistic regression. Weighted Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% CIs for time-to-event endpoints [duration of response (DOR), progression-free survival (PFS), and overall survival (OS)]. RESULTS: After weighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, teclistamab-treated patients were 2.3-fold, 5.2-fold and 148.3-fold, more likely to reach ORR [response-rate ratio (RR) = 2.31, 95% CI 1.77-2.85, p < 0.0001], ≥ VGPR (RR = 5.19, 95% CI 3.26-7.12, p < 0.0001) and ≥ CR (RR = 148.25, 95% CI 20.63-1065.40, p < 0.0001), respectively, versus patients receiving RWPC. Following adjustment, DOR (HR 0.32, 95% CI 0.19-0.54, p < 0.0001) and PFS (HR 0.48, 95% CI 0.35-0.65, p < 0.0001) were significantly longer with teclistamab versus RWPC. OS was numerically better with teclistamab versus RWPC [HR 0.77 (0.55-1.09), p = 0.1419]. CONCLUSION: Teclistamab demonstrated improved effectiveness versus RWPC, highlighting its clinical benefit as a novel and effective treatment for patients with TCE-RRMM. TRIAL REGISTRATION: Majest TEC-1, ClinicalTrials.gov NCT04557098; LocoMMotion, ClinicalTrials.gov NCT04035226.

Contraceptive Continuation and Experiences Obtaining Implant and IUD Removal Among Women Randomized to Use Injectable Contraception, Levonorgestrel Implant, and Copper IUD in South Africa and Zambia.

Few longitudinal studies have measured contraceptive continuation past one year in sub-Saharan Africa. We surveyed 674 women who had been randomized to receive the three-month intramuscular contraceptive injectable (DMPA-IM), levonorgestrel (LNG) implant, or copper intrauterine device (IUD) during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in South Africa and Zambia and were subsequently followed for two additional years to explore method continuation, reasons for discontinuation, and access to implant and IUD removal services. We also conducted in-depth qualitative interviews with 39 participants. We estimated cumulative discontinuation probabilities using Kaplan-Meier estimates and assessed factors associated with discontinuation using Cox-proportional hazards models. The LNG implant continuation rate over the maximum 44-month study period was 60 percent, while rates for the copper IUD and DMPA-IM were 52 percent and 44 percent, respectively. Reasons for method discontinuation included side effects, particularly menstrual changes, and method stock-outs. Most implant and IUD users who sought removal were able to access services; however, room for improvement exists. In this cohort originally randomized to receive a contraceptive method and attend regular study visits, implants and IUDs continued to be highly acceptable over an additional two years, but facilities should continue to ensure that insertions and removals are available as requested.

Is long-acting reversible contraceptive method use associated with HIV testing frequency in KwaZulu-Natal, South Africa and Lusaka, Zambia? Findings from the CUBE study.

Objectives: To assess differences in HIV testing at 6-months intervals over 24 months among intramuscular depot medroxyprogesterone acetate (DMPA-IM) injectable, levonorgestrel implant, or copper intrauterine devices (IUD) users in KwaZulu-Natal, South Africa, and Lusaka, Zambia. Testing at recommended intervals has not been previously assessed in long-acting reversible contraceptive (LARC) users (implant and IUD users) compared to those using effective but shorter-acting methods (such as DMPA-IM) in sub-Saharan Africa. Study design: As part of the longitudinal contraceptive use beyond ECHO (CUBE) study, we measured HIV testing over 24 months. Participants were considered continuous users of DMPA-IM, levonorgestrel implant, or copper IUD if they used the same method across all months of their study participation, or not continuous users of their baseline CUBE method if they switched or discontinued their method. We used multivariable logistic regression models with generalized estimating equations and robust standard errors, stratified by country, to assess differences in HIV testing. Results: Among the 498 participants, HIV testing rates were higher in Zambia for all methods compared to South Africa. In bivariate analyses, continuous implant or IUD users (the LARC users) were significantly less likely to report having received HIV testing at the 6-months and 24-months surveys, compared to continuous DMPA-IM users. In adjusted longitudinal models, continuous IUD users (adjusted odds ratio: 0.42, 95% CI: 0.24, 0.74), continuous implant users (adjusted odds ratio: 0.23, 95% CI: 0.12, 0.42) in South Africa had significantly lower odds of HIV testing compared to continuous DMPA-IM users. There were no significant differences in Zambia in the adjusted models. Conclusion: LARC use may reduce opportunities for HIV testing and users should be counseled on regular HIV testing and the option of HIV self-testing. Implications: Due to infrequent clinical contacts which may lead to lower rates of HIV testing at recommended intervals, LARC users should be provided opportunities to test for HIV at home or when seeking other health services.

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa.

The use of injection drugs in South Africa is increasing. HIV prevention, treatment and addiction services for people who inject drugs (PWID) in South Africa are not well documented. We conducted a mixed-methods study to understand current drug use practices and access to HIV prevention and treatment services for PWID in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who reported injecting opiates within the past 6 months from Durban, KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% of participants living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants reported ever testing for Hepatitis C.

"I am scared, I do not want to lie": Exploring the impacts of COVID-19 on engagement in care, perceived health, relationship dynamics, and parenting among postpartum women with HIV in South Africa.

Background COVID-19 and efforts to manage widespread infection may compromise HIV care engagement. The COVID-19-related factors linked to reduced HIV engagement have not been assessed among postpartum women with HIV, who are at heightened risk of attrition under non-pandemic circumstances. To mitigate the effects of the pandemic on care engagement and to prepare for future public health crises, it is critical to understand how COVID-19 has impacted (1) engagement in care and (2) factors that may act as barriers to care engagement. Methods A quantitative assessment of COVID-19-related experiences was added to a longitudinal cohort study assessing predictors of postpartum attrition from HIV care among women in South Africa. Participants (N = 266) completed the assessment at 6, 12, 18, or 24 months postpartum between June and November of 2020. Those who endorsed one or more challenge related to engagement in care (making or keeping HIV care appointments, procuring HIV medications, procuring contraception, and/or accessing immunization services for infants; n = 55) were invited to complete a brief qualitative interview, which explored the specific factors driving these challenges, as well as other impacts of COVID-19 on care engagement. Within this subset, 53 participants completed an interview; qualitative data were analyzed via rapid analysis. Results Participants described key challenges that reduced their engagement in HIV care and identified four other domains of COVID-19-related impacts: physical health, mental health, relationship with a partner or with the father of the baby, and motherhood/caring for the new baby. Within these domains, specific themes and subthemes emerged, with some positive impacts of COVID-19 also reported (e.g., increased quality time, improved communication with partner, HIV disclosure). Coping strategies for COVID-19-related challenges (e.g., acceptance, spirituality, distraction) were also discussed. Conclusions About one in five participants reported challenges accessing HIV care, medications, or services, and they faced complex, multilayered barriers to remaining engaged. Physical health, mental health, relationships with partners, and ability to care for their infant were also affected. Given the dynamic nature of the pandemic and general uncertainty about its course, ongoing assessment of pandemic-related challenges among postpartum women is needed to avoid HIV care disruptions and to support wellbeing.

Influences on PrEP Uptake and Adherence Among South African Women During Periconception and Pregnancy: A Qualitative Analysis.

Pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, yet PrEP delivery to women in periconception and pregnancy has lagged. We report qualitative research from a study evaluating PrEP use as part of safer conception care for 330 South African women. Fifty-two semi-structured interviews were conducted with 25 study participants to identify influences on PrEP adherence. Influences were: (1) changing proximity to male partners; (2) COVID-19 lockdown; (3) mobile lifestyle; (4) PrEP-related stigma; (5) disclosure of PrEP use; and (6) pregnancy and motherhood. Data also revealed important contextual information shaping adherence influences for women, including: (a) not living with partners, (b) partners as drivers of pregnancy intention, and (c) feeling at high risk for HIV. Disclosure of PrEP use, addressing stigma, strategies for traveling with pills, and counseling on prevention effective adherence are promising components of PrEP-inclusive HIV prevention interventions for South African women who are pregnant or planning pregnancy.