What a Clinician Needs to Know About Genome Editing: Status and Opportunities for Inborn Errors of Immunity.

During the past 20 years, gene editing has emerged as a novel form of gene therapy. Since the publication of the first potentially therapeutic gene editing platform for genetic disorders, increasingly sophisticated editing technologies have been developed. As with viral vector-mediated gene addition, inborn errors of immunity are excellent candidate diseases for a corrective autologous hematopoietic stem cell gene editing strategy. Research on gene editing for inborn errors of immunity is still entirely preclinical, with no trials yet underway. However, with editing techniques maturing, scientists are investigating this novel form of gene therapy in context of an increasing number of inborn errors of immunity. Here, we present an overview of these studies and the recent progress moving these technologies closer to clinical benefit.

Identifying Adolescents at Highest Risk of ART Non-adherence, Using the World Health Organization-Endorsed HEADSS and HEADSS+ Checklists.

Brief tools are necessary to identify adolescents at greatest risk for ART non-adherence. From the WHO's HEADSS/HEADSS+ adolescent wellbeing checklists, we identify constructs strongly associated with non-adherence (validated with viral load). We conducted interviews and collected clinical records from a 3-year cohort of 1046 adolescents living with HIV from 52 South African government facilities. We used least absolute shrinkage and selection operator variable selection approach with a generalized linear mixed model. HEADSS constructs most predictive were: violence exposure (aOR 1.97, CI 1.61; 2.42, p < 0.001), depression (aOR 1.71, CI 1.42; 2.07, p < 0.001) and being sexually active (aOR 1.80, CI 1.41; 2.28, p < 0.001). Risk of non-adherence rose from 20.4% with none, to 55.6% with all three. HEADSS+ constructs were: medication side effects (aOR 2.27, CI 1.82; 2.81, p < 0.001), low social support (aOR 1.97, CI 1.60; 2.43, p < 0.001) and non-disclosure to parents (aOR 2.53, CI 1.91; 3.53, p < 0.001). Risk of non-adherence rose from 21.6% with none, to 71.8% with all three. Screening within established checklists can improve identification of adolescents needing increased support. Adolescent HIV services need to include side-effect management, violence prevention, mental health and sexual and reproductive health.

Using prevention cascades to investigate coverage of contraception services among young women enrolled in a large-scale combination HIV prevention program in South Africa.

OBJECTIVES: We investigated the coverage of contraception services (excluding condoms) to prevent unintended pregnancy among young women and girls aged 15 to 24 years who were beneficiaries of one of the two largest combination HIV and pregnancy prevention program in South Africa. STUDY DESIGN: We invited 2160 randomly sampled beneficiaries who were living in six of the 12 program districts across six provinces to participate in a telephone survey. We created pregnancy prevention coverage cascades and conducted univariate and multivariable analyses to identify key barriers and facilitators associated with each step of the cascade. RESULTS: We achieved a response rate of 23.8%, resulting in 515 respondents, of whom 303 had sex in the 6 months before the survey. Of this subsample, 80.4% had access to contraception services, 60.6% had access and motivation to use contraceptives, and 21.9% had access to, motivation to use, and effectively used contraceptives. Distance to travel to services and not ever being offered contraceptives by health workers were access barriers, while low pregnancy risk perception was a barrier to motivation. CONCLUSIONS: Most respondents had access to and were motivated to use contraceptives other than condoms but were not effectively using them. Having been offered contraceptives facilitated better access, while distance to the services was a barrier, suggesting the importance of improving supply-side interventions, such as increasing the number and accessibility of spaces where Sexual and Reproductive Health (SRH) services are offered. We recommend longitudinal behavioral counseling for young people, especially adolescents, as well as risk reduction and information-tailored interventions. IMPLICATIONS: Pregnancy prevention cascades are a promising tool to monitor progress toward universal access to contraception services and to identify barriers that need to be addressed to achieve the effective use of contraceptives.

Better Together: acceptability, feasibility and preliminary impact of chronic illness peer support groups for South African adolescents and young adults.

INTRODUCTION: Peer support can help navigate the isolation and psychological strain frequently experienced by youth living with chronic illness. Yet, data are lacking on the impact of providing support for youth living with mixed chronic conditions. We assessed the acceptability, feasibility and preliminary mental health impacts of a clinic-based peer support group for South African youth living with chronic illnesses, including HIV. METHODS: This mixed-methods pilot study (September 2021-June 2022) enrolled 58 young patients, ages 13-24, at an urban hospital in Cape Town, South Africa. In-depth interviews elicited the perspectives of 20 young people in relation to their participation in the Better Together programme, a recurring clinic-based peer support group for patients with mixed chronic illnesses. Self-reported resilience, attitudes towards illness, stigma and mental health were captured via established measures. T-tests and multivariate analysis of variance compared psychosocial outcomes for 20 group participants and 38 control patients, controlling for socio-demographic characteristics at enrolment. Logistic regression analyses estimated the predicted probability of a positive depression or anxiety screening given peer group participation. RESULTS: All interviewees valued being able to compare treatment regimens and disease management habits with peers living with different conditions. Adolescents living with HIV stated that understanding the hardships faced by those with other conditions helped them accept their own illness and lessened feelings of isolation. Compared to patients who did not participate in Better Together, those who attended ≥5 groups had statistically significantly higher individual-level resilience, a more positive attitude towards their illness(es), lower internalised stigma and a more positive self-concept. The probability of being screened positive for depression was 23.4 percentage points lower (95% CI: 1.5, 45.3) for Better Together participants compared to controls; the probability of a positive anxiety screening was 45.8 percentage points lower (95% CI: 18.1, 73.6). CONCLUSIONS: Recurring, clinic-based peer support groups that integrate youth living with HIV and other chronic diseases are novel. Group sustainability will depend on the commitment of experienced peer leaders and providers, routine scheduling and transportation support. A fully powered randomised trial is needed to test the optimal implementation and causal mental health effects of the Better Together model.

Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI): Developing Career Pathways for Early-Stage Scholars From Racial and Ethnic Groups Underrepresented in HIV Science and Medicine.

BACKGROUND: There is an urgent need to increase diversity among scientific investigators in the HIV research field to be more reflective of communities highly affected by the HIV epidemic. Thus, it is critical to promote the inclusion and advancement of early-stage scholars from racial and ethnic groups underrepresented in HIV science and medicine. METHODS: To widen the HIV research career pathway for early-stage scholars from underrepresented minority groups, the National Institutes of Health supported the development of the Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI). This program was created through partnerships between CFARs and Historically Black Colleges and Universities and other Minority Serving Institutions throughout the United States. RESULTS: Seventeen CFARs and more than 20 Historically Black Colleges and Universities and Minority Serving Institutions have participated in this initiative to date. Programs were designed for the high school (8), undergraduate (13), post baccalaureate (2), graduate (12), and postdoctoral (4) levels. Various pedagogical approaches were used including didactic seminar series, intensive multiday workshops, summer residential programs, and mentored research internship opportunities. During the first 18 months of the initiative, 257 student scholars participated in CDEIPI programs including 150 high school, 73 undergraduate, 3 post baccalaureate, 27 graduate, and 4 postdoctoral students. CONCLUSION: Numerous student scholars from a wide range of educational levels, geographic backgrounds, and racial and ethnic minority groups have engaged in CDEIPI programs. Timely and comprehensive program evaluation data will be critical to support a long-term commitment to this unique training initiative.

Examining Associations Between Resilience and Sexual Health Among South African Girls and Young Women Living With and Without HIV.

Resilience, or multilevel processes related to thriving, offers a strengths-based approach to reducing HIV and sexual risk behaviors among girls and young women. Processes of resilience may change based on the experience of living with HIV. However, little is known about how resilience and serologically verified HIV status influence sexual health. Using weighted cross-sectional data collected during 2017-2018 from South African girls and young women aged 15-24 (N = 7237), this article examines associations between resilience and three sexual risk behaviors among those living with and without HIV. Logistic regression models indicated greater resilience scores were associated with reduced odds of engaging in transactional sex and early sexual debut. Results also identified differing associations between resilience and sexual risk behaviors by HIV status. Findings provide implications for programming to prevent HIV and improve sexual health while underscoring the need for tailored resilience-promoting interventions for South African girls and young women living with HIV.

Subjective experiences, contexts, and risk perceptions of very low nicotine content cigarettes and electronic cigarettes among people with depression and anxiety disorders who smoke.

BACKGROUND: A low-nicotine product standard is currently under consideration by the U.S. Food and Drug Administration (FDA). This standard may be more effective if alternative, non-combusted sources of nicotine are concurrently available. This qualitative study explored the lived experiences of people with depression and anxiety disorders who used very low nicotine content (VLNC) cigarettes with or without e-cigarettes during a randomized controlled trial. METHODS: We conducted semi-structured qualitative interviews with participants (n = 20) as they completed a 16-week blinded trial of VLNC cigarettes with or without electronic cigarettes. Interviews explored 1) experiences with these products, 2) social and environmental contexts for use and 3) relative risk perceptions. Interviews were transcribed and analyzed using a hybrid inductive and deductive thematic analysis. RESULTS: Concurrent access to e-cigarettes helped to ease the transition from usual-brand cigarettes to VLNC cigarettes. Some participants held misperceptions that VLNC cigarettes could reduce cancer risk whereas others did not. Participants expressed skepticism about the safety of e-cigarettes and the authenticity of the VLNC cigarettes. Smoking restrictions influenced e-cigarette use in some instances, but product preference was the overriding factor that influenced use. Participants did not note effects on psychiatric symptoms. CONCLUSIONS: Should a nicotine reduction policy be implemented with e-cigarettes concurrently available on the market, tailored messaging for people with anxiety and depression disorders may be necessary to educate people about and the availability of alternative sources of nicotine, such as e-cigarettes, as well as the relative risk of VLNC cigarettes and e-cigarettes.

Understanding Oral Prep Interest Among South African Adolescents: The Role of Perceived Parental Support and PrEP Stigma.

We examined oral PrEP interest among adolescents and its association with perceived parental support and PrEP stigma. Cross-sectional data were collected during baseline procedures of the "Our Family Our Future" intervention trial in South Africa. Adolescents (14-16 years) at elevated risk for acquiring HIV and their parents or caregivers were dyadically enrolled from 2018 to 2021. There were 879 complete adolescent-parent dyads. Among adolescents, 27% had heard about PrEP, 67% reported they would want to use PrEP, and 58% thought their parent would want them to use PrEP. Among parents, 33% had heard about PrEP and 85% reported they would want their adolescent to use PrEP. Adolescents who thought their parent would want them to use PrEP were more likely to be interested in PrEP than adolescents who thought their parent would not want them to use PrEP (adjusted prevalence ratio (aPR) = 2.11, 95% CI 1.82, 2.44). Further, adolescents with higher average PrEP stigma scores above the adolescent sample median were less likely to be interested in PrEP than adolescents with lower average PrEP stigma scores (aPR = 0.81, 95% CI 0.72, 0.91). In conclusion, parents were more supportive of their adolescent taking PrEP than adolescents perceived they would be, and perceptions of low parental support and greater PrEP stigma were associated with reduced PrEP interest among adolescents. Interventions should aim to improve adolescent-parent communication around sexual health and effective HIV prevention tools.

Immunotherapy responsive neuroinflammation in a child with FAS-associated death-domain mutation.

Death-inducing signaling complex (DISC), FAS-associated death-domain-containing protein (FADD), Fas receptor (FASR), Fas ligand (FASL).

Social resources, resilience, and sexual health among South African adolescent girls and young women: findings from the HERStory study.

Socioecological factors, including social resources, influence South African adolescent girls' and young women's sexual health. Few studies have explored how these multi-level social factors relate to both resilience and sexual health in this community. This study examines if social resources mediate associations between resilience and two sexual health outcomes. A weighted-sample of 7,237 South African girls and young women (aged 15-24 years) completed a cross-sectional survey conducted from 2017 to 2018 which included a validated measure of resilience, along with measures of sexual health and social resources. Using multivariable logistic regression models and bootstrapping methods, two types of social resources were assessed as potential mediators. Increased resilience was negatively associated with early sexual debut and engagement in transactional sex. Social support mediated associations between resilience and engagement in transactional sex but did not mediate associations between resilience and early sexual debut. Of all the types of social support measured, social support from a special person mediated the largest proportion of the association between resilience and transactional sex. Examining underlying social and community dynamics related to resilience and sexual health can guide the development of future contextually-relevant programming and policies.

Lentiviral Gene Therapy for Artemis-Deficient SCID.

BACKGROUND: The DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in DCLRE1C, which encodes Artemis, cause Artemis-deficient severe combined immunodeficiency (ART-SCID), which is poorly responsive to allogeneic hematopoietic-cell transplantation. METHODS: We carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing DCLRE1C, in 10 infants with newly diagnosed ART-SCID. We followed them for a median of 31.2 months. RESULTS: Marrow harvest, busulfan conditioning, and lentiviral-transduced CD34+ cell infusion produced the expected grade 3 or 4 adverse events. All the procedures met prespecified criteria for feasibility at 42 days after infusion. Gene-marked T cells were detected at 6 to 16 weeks after infusion in all the patients. Five of 6 patients who were followed for at least 24 months had T-cell immune reconstitution at a median of 12 months. The diversity of T-cell receptor ß chains normalized by 6 to 12 months. Four patients who were followed for at least 24 months had sufficient B-cell numbers, IgM concentration, or IgM isohemagglutinin titers to permit discontinuation of IgG infusions. Three of these 4 patients had normal immunization responses, and the fourth has started immunizations. Vector insertion sites showed no evidence of clonal expansion. One patient who presented with cytomegalovirus infection received a second infusion of gene-corrected cells to achieve T-cell immunity sufficient for viral clearance. Autoimmune hemolytic anemia developed in 4 patients 4 to 11 months after infusion; this condition resolved after reconstitution of T-cell immunity. All 10 patients were healthy at the time of this report. CONCLUSIONS: Infusion of lentiviral gene-corrected autologous CD34+ cells, preceded by pharmacologically targeted low-exposure busulfan, in infants with newly diagnosed ART-SCID resulted in genetically corrected and functional T and B cells. (Funded by the California Institute for Regenerative Medicine and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03538899.).

"We Should Be Taught Self-Respect, Self-Confidence and Self-Love": Youth Perspectives of Adult Influences on Their Sexuality and Relationships Among South African Adolescents Living With HIV.

Introduction: Of the 1.75 million adolescents aged 10-19 years living with HIV globally, 84% reside in sub-Saharan Africa. This problem is most acute in South Africa, where there are 720,000 adolescents living with HIV (ALHIV). ALHIV navigate the same challenges as other adolescents-such as puberty and first relationships-as well as challenges specific to their HIV-status-including stigma, disclosure, and concerns about HIV transmission. This dual burden calls for tailored sexual and reproductive health (SRH) programs. Here, we qualitatively explore the reflections of South African ALHIV on SRH education, communication, and discussion provided by adults in schools, clinics, and the home related to their unique SRH needs. Methods: This paper reports on qualitative data from a mixed-methods study to inform interventions that meet the SRH needs of ALHIV. In-depth interviews (N = 20) were conducted with ALHIV recruited from two clinics in Cape Town, South Africa. Nine males and 11 females aged 16-19 participated in semi-structured in-depth interviews to discuss their sexual health as ALHIV. The interview guide explored 1) perceived SRH needs; 2) healthy living with HIV; 3) future goals; 4) intimate relationships; 5) psychosocial challenges; and 6) preferred interventions. Data were thematically applied to an iteratively-developed codebook and analyzed by the cross-cultural research team using NVivo 12. Results: These qualitative data reveal the pressing needs among ALHIV for open communication and accurate information about sexuality and HIV, given the risk to themselves and their partners as they enter intimate relationships. Three themes emerged from the data: 1) Intergenerational pressures coming from caregivers, clinicians, and teachers often stigmatize the sexual heath behaviors of ALHIV; 2) When present, open intergenerational communication can provide ALHIV with crucial information, resources, and social support that supports healthy decisions, and 3) ALHIV offer specific ideas about how adults can support their decision-making in the transition to adulthood. Conclusions: Findings highlight adolescents' recommendations for programs involving open communication, stigma-reduction around sexuality, and support from both peer and adult mentors. This study lays the foundation for strategies to improve intergenerational communication about sexual health to promote positive approaches to sexuality for ALHIV.

Food security reduces multiple HIV infection risks for high-vulnerability adolescent mothers and non-mothers in South Africa: a cross-sectional study.

INTRODUCTION: Adolescent girls and young women, including adolescent mothers, in Southern Africa have high HIV seroconversion and transmission. We need to know which risks drive HIV infections, and what can reduce these risks. METHODS: We interviewed 1712 adolescent girls and young women (11-23 years), including 1024 adolescent mothers who had conceived before age 20 and had a living child, from two health municipalities of South Africa's Eastern Cape Province between March 2018 and July 2019. Recruitment was through multiple community, school and health facility channels. Associations between adolescent motherhood and seven HIV risk behaviours (multiple sexual partners, transactional sex, age-disparate sex, condomless sex, sex on substances, alcohol use and not in education or employment) were investigated using the generalized estimating equations method for multiple outcomes specified with a logit link and adjusting for nine covariates. Using the same model, we investigated associations between having enough food at home every day in the past week (food security) and the same seven HIV risk behaviours. When we found evidence of moderation by HIV status, we report stratum-specific odds ratios. RESULTS: Mean age was 17.51 years (SD: 2.54), 46% participants were living with HIV. Compared to non-mothers, adolescent mothers had lower odds of alcohol use (AOR = 0.47, 95% CI = 0.29-0.75), but higher odds of multiple sexual partners (AOR = 1.93, 95% CI = 1.35-2.74), age-disparate sex (HIV-uninfected AOR = 1.73, 95% CI = 1.03-2.91; living with HIV AOR = 5.10, 95% CI = 2.98-8.73), condomless sex (AOR = 8.20, 95% CI = 6.03-11.13), sex on substances (AOR = 1.88, 95% CI = 1.10-3.21) and not in education/employment (HIV-uninfected AOR = 1.83, 95% CI = 1.19-2.83; living with HIV AOR = 6.30, 95% CI = 4.09-9.69). Among non-mothers, food security was associated with lower odds of multiple sexual partners (AOR = 0.45, 95% CI = 0.26-0.78), transactional sex (AOR = 0.32, 95% CI = 0.13-0.82) and not in education/employment (AOR = 0.48, 95% CI = 0.29-0.77). Among adolescent mothers, food security was associated with lower odds of transactional sex (AOR = 0.17, 95% CI = 0.10-0.28), age-disparate sex (AOR = 0.66, 95% CI = 0.47-0.92), sex on substances (AOR = 0.51, 95% CI = 0.32-0.82), alcohol use (AOR = 0.45, 95% CI = 0.25-0.79) and not in education/employment (AOR = 0.56, 95% CI = 0.40-0.78). CONCLUSIONS: Adolescent motherhood is associated with multiple vulnerabilities to HIV infection and transmission. Social protection measures that increase food security are likely to reduce HIV risk pathways for adolescent girls and young women, especially adolescent mothers.

Participation in an HIV prevention intervention and access to and use of contraceptives among young women: A cross sectional analysis in six South African districts.

OBJECTIVE: This study investigated whether young women's participation in a combination HIV-prevention intervention was associated with accessing and using condoms and other contraceptives. STUDY DESIGN: A cross-sectional household survey was conducted from 2017 to 2018 among a representative sample of young women aged 15-24 years old living in six South African districts in which the intervention was implemented. Cross-tabulations and multivariate regression analyses of weighted data were performed to examine access to and use of condoms and other contraceptives. RESULTS: In total 4399 young women participated, representing a 60.6% response rate. Of participants, 61.0% (n = 2685) reported accessing condoms and other contraceptives in the past year. Among those who ever had sex (n = 3009), 51.0% used condoms and 37.4% other contraceptives at last sex. Among 15-19 year old, participation in the combination intervention was positively associated with reporting contraceptive use other than condoms at last sex (Prevalence Ratio (PR): 1.36; 95% CI: 1.21-1.53) and reporting use of both condoms and other contraceptives at last sex (PR: 1.45; 95% CI: 1.26-1.68). No associations were observed in the age group 20-24. CONCLUSION: Our findings suggest that combination HIV prevention interventions may lead to increased access and use of condoms and other methods of contraception among adolescent women, but this needs to be confirmed in experimental studies. We need to test different or more intensive interventions to increase contraceptive use in young women aged 20-24. IMPLICATIONS: Participating in combination HIV prevention interventions that are delivered via multiple approaches may promote access to, and use of condoms and other methods of contraceptives among adolescent women, and thereby help reduce unintended pregnancies.

Conditional Economic Incentives for HIV Treatment Adherence: Aligning Adolescent Developmental Hallmarks with Behavioral Economic Theory to Improve HIV Treatment Adherence.

Adolescent-tailored antiretroviral therapy (ART) adherence interventions take place within the context of unique developmental stage. Suboptimal ART adherence among adolescents living with HIV in South Africa underscores that interventions are urgently needed to improve adherence. We conducted semistructured in-depth interviews with 35 adolescents aged 10-19 years living with HIV. In addition, 14 clinicians and 35 caregivers were interviewed to provide a diverse perspective on barriers and facilitators of medication adherence for adolescents living with HIV (ALWH). Thematic coding was utilized for this analysis. Our main findings were organized by following a priori themes: (1) acceptability of conditional economic incentives (CEIs) as an adherence intervention strategy for adolescents, (2) predicted behavioral impacts, and the (3) durability of CEIs to ensure medication adherence for adolescents in the long term. Subthemes that emerged included CEIs as tool to overcome competing demands, increasing intrinsic motivation and orientation toward the future, and optimal timing of the intervention. Exposure to a CEI intervention during early adolescence (ages 10-13) may be a particularly helpful intervention as CEIs may have long-lasting effects given that habit-formation behavior is developed during early adolescence. There is little consensus on effect duration from the perspective of adolescents, clinicians, and caregivers. Future studies should continue to explore the impact of CEIs for long-term ART adherence.

Genes as Medicine: The Development of Gene Therapies for Inborn Errors of Immunity.

The field of gene therapy has experienced tremendous growth in the last decade ranging from improvements in the design of viral vectors for gene addition of therapeutic gene cassettes to the discovery of site-specific nucleases targeting transgenes to desired locations in the genome. Such advancements have not only enabled the development of disease models but also created opportunities for the development of tailored therapeutic approaches. There are 3 main methods of gene modification that can be used for the prevention or treatment of disease. This includes viral vector-mediated gene therapy to supply or bypass a missing/defective gene, gene editing enabled by programmable nucleases to create sequence-specific alterations in the genome, and gene silencing to reduce the expression of a gene or genes. These gene-modification platforms can be delivered either in vivo, for which the therapy is injected directed into a patient's body, or ex vivo, in which cells are harvested from a patient and modified in a laboratory setting, and then returned to the patient.

Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC.

Adenosine deaminase (ADA) deficiency causes ∼13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 patients with ADA-SCID diagnosed between 1982 and 2017 who were enrolled in the Primary Immune Deficiency Treatment Consortium SCID studies. Baseline clinical, immunologic, genetic characteristics, and treatment outcomes were analyzed. First definitive cellular therapy (FDCT) included 56 receiving HCT without preceding ERT (HCT); 31 HCT preceded by ERT (ERT-HCT); and 33 GT preceded by ERT (ERT-GT). Five-year event-free survival (EFS, alive, no need for further ERT or cellular therapy) was 49.5% (HCT), 73% (ERT-HCT), and 75.3% (ERT-GT; P < .01). Overall survival (OS) at 5 years after FDCT was 72.5% (HCT), 79.6% (ERT-HCT), and 100% (ERT-GT; P = .01). Five-year OS was superior for patients undergoing HCT at <3.5 months of age (91.6% vs 68% if ≥3.5 months, P = .02). Active infection at the time of HCT (regardless of ERT) decreased 5-year EFS (33.1% vs 68.2%, P < .01) and OS (64.7% vs 82.3%, P = .02). Five-year EFS (90.5%) and OS (100%) were best for matched sibling and matched family donors (MSD/MFD). For patients treated after the year 2000 and without active infection at the time of FDCT, no difference in 5-year EFS or OS was found between HCT using a variety of transplant approaches and ERT-GT. This suggests alternative donor HCT may be considered when MSD/MFD HCT and GT are not available, particularly when newborn screening identifies patients with ADA-SCID soon after birth and before the onset of infections. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.

'I can't go to her when I have a problem': sexuality communication between South African adolescent girls and young women and their mothers.

Parent-adolescent sexuality communication, the process in which parents and their adolescent children discuss sexuality and sexual and reproductive health, is a key component for adolescents' protective behaviours. Open communication with parents, particularly mothers, enables informed sexual and reproductive health (SRH) decision-making amongst adolescent girls and young women (AGYW). As part of a qualitative study evaluating a South African combination HIV prevention intervention for AGYW, we explored perspectives on SRH communication among AGYW and mothers of AGYW, and the effects of the intervention on sexuality communication as perceived by AGYW, mothers of AGYW, intervention facilitators and implementers, and community leaders. In-depth interviews and focus group discussions were conducted with 185 AGYW aged 15-24 years who had participated in the intervention, seven mothers of AGYW intervention recipients, 14 intervention facilitators, six community leaders, and 12 intervention implementers. Key themes that emerged in analysis were (1) Barriers to Sexuality communication, (2) Implications of Gaps in Sexuality Communication, and (3) Addressing Barriers to Sexuality communication. Barriers to sexuality communication included inability or unwillingness to discuss sex, a generation gap, proscriptive socio-cultural guidelines, and mothers' discomfort, lack of knowledge and self-efficacy, and fear of encouraging promiscuity. AGYW described making poorly-informed SRH decisions alone, expressing a desire for more open communication with and support from parents/mothers. Framed within the social cognitive theory, these findings can help to guide efforts to address barriers around parent-adolescent sexuality communication, inform interventions aimed at targeting SRH issues amongst AGYW, such as unintended pregnancy and HIV, and support meaningful engagement of parents in supporting AGYW in navigating pathways to achieving their SRH goals.