Association between monocyte-to-lymphocyte ratio and tuberculin skin test positivity in HIV-positive adults.

BACKGROUND: The tuberculin skin test (TST) identifies individuals at high risk of developing tuberculosis (TB) but poses many challenges. The blood monocyte-to-lymphocyte ratio (MLR) could be an alternative, as extremes in MLR have been associated with increased risk of TB disease. METHODS: At a primary care clinic in Johannesburg, a differential white blood cell count and TST was performed in adults starting antiretroviral treatment (ART) without symptoms suggestive of active TB. RESULTS: Of 259 participants, 171 had valid results of whom 30% (51/171) were TST positive and the median MLR was 0.18 (IQR 0.13-0.28). The MLR distribution differed between CD4 count categories (p < 0.01), with a broader range of values in TST negative participants with a low CD4 count (≤ 250 cells/mm3), likely reflecting HIV immunosuppression. MLR was associated with a positive TST (OR 0.78 per 0.1 increase, 95% CI 0.59, 0.97) in bivariate analysis but not in multivariate regression analysis (aOR 0.83 for every 0.1 increase, 95% CI 0.60, 1.08). CONCLUSION: In ART-naïve adults without symptoms suggestive of active TB, MLR was not independently associated with TST positivity and is thus unlikely to be a useful alternative to TST. Future research should focus on development of a cheap, simple and accurate biomarker to identify those people benefiting most from preventive TB therapy.

High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care.

OBJECTIVES: Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce. METHODS: To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment). RESULTS: Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/µl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/µl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/µl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/µl (50/100 person-years, 95% CI 32, 73). CONCLUSIONS: TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/µl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.

Attitudes Toward a Proposed GPS-Based Location Tracking Smartphone App for Improving Engagement in HIV Care Among Pregnant and Postpartum Women in South Africa: Focus Group and Interview Study.

BACKGROUND: Peripartum women living with HIV in South Africa are at high risk of dropping out of care and are also a particularly mobile population, which may impact their engagement in HIV care. With the rise in mobile phone use worldwide, there is an opportunity to use smartphones and GPS location software to characterize mobility in real time. OBJECTIVE: The aim of this study was to propose a smartphone app that could collect individual GPS locations to improve engagement in HIV care and to assess potential users' attitudes toward the proposed app. METHODS: We conducted 50 in-depth interviews (IDIs) with pregnant women living with HIV in Cape Town and Johannesburg, South Africa, and 6 focus group discussions (FGDs) with 27 postpartum women living with HIV in Cape Town. Through an open-ended question in the IDIs, we categorized "positive," "neutral," or "negative" reactions to the proposed app and identified key quotations. For the FGD data, we grouped the text into themes, then analyzed it for patterns, concepts, and associations and selected illustrative quotations. RESULTS: In the IDIs, the majority of participants (76%, 38/50) responded favorably to the proposed app. Favorable comments were related to the convenience of facilitated continued care, a sense of helpfulness on the part of the researchers and facilities, and the difficulties of trying to maintain care while traveling. Among the 4/50 participants (8%) who responded negatively, their comments were primarily related to the individual's responsibility for their own health care. The FGDs revealed four themes: facilitating connection to care, informed choice, disclosure (intentional or unintentional), and trust in researchers. CONCLUSIONS: Women living with HIV were overwhelmingly positive about the idea of a GPS-based smartphone app to improve engagement in HIV care. Participants reported that they would welcome a tool to facilitate connection to care when traveling and expressed trust in researchers and health care facilities. Within the context of the rapid increase of smartphone use in South Africa, these early results warrant further exploration and critical evaluation following real-world experience with the app.

Novel health system strategies for tuberculin skin testing at primary care clinics: Performance assessment and health economic evaluation.

BACKGROUND: Tuberculin skin test (TST) for guiding initiation of tuberculosis preventive therapy poses major challenges in high tuberculosis burden settings. METHODS: At a primary care clinic in Johannesburg, South Africa, 278 HIV-positive adults self-read their TST by reporting if they felt a bump (any induration) at the TST placement site. TST reading (in mm) was fast-tracked to reduce patient wait time and task-shifted to delegate tasks to lower cadre healthcare workers, and result was compared to TST reading by high cadre research staff. TST reading and placement cost to the health system and patients were estimated. Simulations of health system costs were performed for 5 countries (USA, Germany, Brazil, India, Russia) to evaluate generalizability. RESULTS: Almost all participants (269 of 278, 97%) correctly self-identified the presence or absence of any induration [sensitivity 89% (95% CI 80,95) and specificity 99.5% (95% CI 97,100)]. For detection of a positive TST (induration ≥ 5mm), sensitivity was 90% (95% CI 81,96) and specificity 99% (95% CI 97,100). TST reading agreement between low and high cadre staff was high (kappa 0.97, 95% CI 0.94, 1.00). Total TST cost was 2066 I$ (95% UI 594, 5243) per 100 patients, 87% (95% UI 53, 95) of which were patient costs. Combining fast-track and task-shifting, reduced total costs to 1736 I$ (95% UI 497, 4300) per 100 patients, with 31% (95% UI 15, 42) saving in health system costs. Combining fast-tracking, task-shifting and self-reading, lowered the TST health system costs from 16% (95% UI 8, 26) in Russia to 40% (95% UI 18, 54) in the USA. CONCLUSION: A TST strategy where only patients with any self-read induration are asked to return for fast-tracked TST reading by lower cadre healthcare workers is a promising strategy that could be effective and cost-saving, but real-life cost-effectiveness should be further examined.

Home-based delivery of HIV self-tests by adolescent girls and young women to male sexual partners in Johannesburg, South Africa: benefits and concerns.

There is limited information about the best strategy for adolescent girls and young women (AGYW) to negotiate HIV testing with their male partners. HIV self-testing as a strategy has the potential to overcome barriers to traditional HIV testing among men. We conducted formative feasibility research on secondary distribution of HIV self-tests by HIV negative AGYW to their male partners in northern Johannesburg, South Africa. A total of 8 focus group discussions with AGYW and men and 20 key informant interviews with community stakeholders were conducted to determine the best approach to partner-initiated testing. This study suggested that AGYW-initiated secondary distribution of HIV self-testing to their male sexual partners is considered an acceptable strategy by AGYW, men, and the community at large. The benefits included empowerment of women, reduction in HIV-testing associated stigma, and increased privacy and confidentiality for the men who test. Major concerns were safety of the AGYW, safety of men testing positive at home, and the lack of pre- and post-test counseling. The outcomes of the formative research were used to refine strategies for a secondary distribution of HIV self-testing intervention.

Sexual Relationship Types, Partner HIV Self-Testing, and Pre-Exposure Prophylaxis Among South African Adolescent Girls and Young Women: A Latent Class Analysis.

BACKGROUND: Sexual relationships among adolescent girls and young women (AGYW) are influenced by social, economic, and gender dynamics. Understanding AGYW's different relationship types and their implications for HIV risk is important for development of tailored interventions. We sought to identify relationship typologies among AGYW and their impact on uptake of HIV prevention interventions. METHODS: From May 2018 to February 2019, 2200 HIV-negative AGYW (ages 16-24) in Johannesburg, South Africa, participated in an HIV prevention intervention involving distribution of HIV self-test kits to their male partners. AGYW were also offered pre-exposure prophylaxis. At baseline, AGYW completed a questionnaire, and outcomes were assessed for 3 months. We used latent class analysis to identify relationship types and mixture modeling to estimate the impact of relationship type on engagement in prevention interventions. RESULTS: We identified 3 relationship types: "stable, empowered relationships with older partners" (class 1, n = 973); "shorter, empowered relationships with peer partners" (class 2, n = 1067); and "shorter relationships with risky partners" (class 3, n = 160). Compared with AGYW in class 1 relationships, AGYW in class 2 and 3 relationships were less likely to complete partner testing alongside HIV results sharing (class 2 adjusted risk ratio: 0.89, 95% confidence interval: 0.85 to 0.95; class 3 adjusted risk ratio: 0.84, 95% confidence interval: 0.73 to 0.94). Pre-exposure prophylaxis uptake was highest in class 3 (11.2%) compared with class 2 (3.8%) and class 1 (1.0%; P < 0.001). CONCLUSIONS: Relationship type impacts uptake of HIV prevention interventions among South African youth. Intervention effectiveness could be optimized by using tailored approaches to HIV risk mitigation among AGYW.

Qualitative characterizations of relationships among South African adolescent girls and young women and male partners: implications for engagement across HIV self-testing and pre-exposure prophylaxis prevention cascades.

INTRODUCTION: Adolescent girls and young women (AGYW) in sub-Saharan Africa have emerged as a priority population in need of HIV prevention interventions. Secondary distribution of home-based HIV self-test kits by AGYW to male partners (MP) is a novel prevention strategy that complements pre-exposure prophylaxis (PrEP), a female-controlled prevention intervention. The objective of this analysis was to qualitatively operationalize two HIV prevention cascades through the lens of relationship dynamics for secondary distribution of HIV self-tests to MP and PrEP for AGYW. METHODS: From April 2018 to December 2018, 2200 HIV-negative AGYW aged 16-24 years were enrolled into an HIV prevention intervention which involved secondary distribution of self-tests to MP and PrEP for AGYW; of these women, 91 participants or MP were sampled for in-depth interviews based on their degree of completion of the two HIV prevention cascades. A grounded theory approach was used to characterize participants' relationship profiles, which were mapped to participants' engagement with the interventions. RESULTS: In cases where AGYW had a MP with multiple partners, AGYW perceived both interventions as inviting distrust into the relationship and insinuating non-monogamy. Many chose not to accept either intervention, while others accepted and attempted to deliver the self-test kit but received a negative reaction from their MP. In the few cases where AGYW held multiple partnerships, both interventions were viewed as mechanisms for protecting one's health, and these AGYW exhibited confidence in accepting and delivering the self-test kits and initiating PrEP. Women who indicated intimate partner violence experiences chose not to accept either intervention because they feared it would elicit a violent reaction from their MP. For AGYW in relationships described as committed and emotionally open, self-test kit delivery was completed with ease, but PrEP was viewed as unnecessary. MP experience with the cascade corroborated AGYW perspectives and demonstrated how men can perceive female-initiated HIV prevention options as beneficial for AGYW and a threat to MP masculinity. CONCLUSIONS: Screening to identify AGYW relationship dynamics can support tailoring prevention services to relationship-driven barriers and facilitators. HIV prevention counseling for AGYW should address relationship goals or partner's influence, and engage with MP around female-controlled prevention interventions.

Perceptions of Community and Clinic-Based Adherence Clubs for Patients Stable on Antiretroviral Treatment: A Mixed Methods Study.

Adherence clubs for patients stable on antiretroviral treatment (ART) offer decongestion of clinics and task-shifting, improved adherence and retention in care. Findings on patient acceptability by club location (in the clinic vs. the community) are limited. This was a mixed-methods study set within a randomized controlled trial of community versus clinic-based adherence clubs for retention in care at Witkoppen Health and Welfare Centre in Johannesburg, South Africa. Participants were surveyed on preferences for adherence club-based care (e.g. location, convenience). We conducted in-depth interviews (IDIs) with 36 participants, and surveyed 568 participants: 49% in community-based clubs and 51% in clinic-based clubs. Participants in both arms favorably rated adherence clubs. Almost all (95%) in clinic-based clubs would recommend them to a friend, while fewer (88% in community-based club participants would do so (p = 0.004). Participants found clubs promoted social support, and were convenient and time-saving, though concerns around stigma and access to other health care were noted within community-based clubs. Adherence clubs are a highly acceptable form of differentiated care for stable ART patients. These data indicate that clinic-based clubs may be preferred above community-based clubs, potentially for reasons of stigma and access to additional health care services.

Psychiatric Comorbidity of Unipolar Mood, Anxiety, and Trauma Disorders Prior to HIV Testing and the Effect on Linkage to Care Among HIV-Infected Adults in South Africa.

Psychiatric comorbidity, the presence of two or more psychiatric disorders, leads to worse HIV outcomes in the United States; this relationship has not been studied in sub-Saharan Africa. We conducted a preliminary study to describe the prevalence of psychiatric comorbidity (unipolar mood, anxiety, and trauma disorders) among 363 adults prior to HIV testing at Witkoppen Health and Welfare Centre, a primary care clinic in Johannesburg, South Africa. We also examined whether psychiatric comorbidity predicted subsequent linkage to HIV care 3 months later. Prevalence of psychiatric comorbidity prior to HIV testing was approximately 5.5%. In the final HIV-positive subsample (n = 76), psychiatric comorbidity of unipolar mood, anxiety, and trauma disorders did not predict linkage to care [adjusted relative risk = 1.01 (0.59, 1.71)] or number of follow-up appointments (adjusted relative risk = 0.86 (0.40, 1.82)]. A similar psychiatric profile emerged for HIV-positive and HIV-negative individuals before becoming aware of their HIV status. The psychiatric burden typically seen in HIV-positive individuals may manifest over time.

Acceptability of Interventions to Improve Engagement in HIV Care Among Pregnant and Postpartum Women at Two Urban Clinics in South Africa.

INTRODUCTION: Pregnant women initiating antiretroviral therapy (ART) in sub-Saharan Africa have been shown to have sub-optimal engagement in care, particularly after delivery, and interventions to improve engagement in care for this unique population are urgently needed. METHODS: We enrolled 25 pregnant women living with HIV at each of two large antenatal clinics in Johannesburg and Cape Town, South Africa (n = 50), and conducted in-depth interviews. We assessed participants' reported acceptability of the following proposed interventions to improve engagement in care and retention monitoring data systems: financial incentives, educational toys, health education, combined maternal/infant visits, cell phone text reminders, mobility tracking, fingerprint/biometric devices, and smartcards. RESULTS: Acceptability overall for interventions was high, with mixed responses for some interventions. Overall themes identified included (i) the intersection of individual and facility responsibility for a patient's health, (ii) a call for more health education, (iii) issues of disclosure and concerns about privacy, and (iv) openness to interventions that could improve health systems. DISCUSSION: These findings provide insight into the preferences and concerns of potential users of interventions to improve engagement in HIV care for pregnant women, and support the development of tools that specifically target this high-risk group.

HIV incidence, pregnancy, and implementation outcomes from the Sakh'umndeni safer conception project in South Africa: a prospective cohort study.

BACKGROUND: Safer conception strategies empower individuals trying to conceive to minimise HIV transmission risk to partners and potential children; however, effectiveness data are scarce. We aimed to assess adoption of safer conception methods and HIV and pregnancy outcomes from Sakh'umndeni, a novel safer conception service in South Africa. METHODS: In this prospective cohort study, the Sakh'umndeni clinical cohort at Witkoppen Cinic in Johannesburg (South Africa) enrolled adults aged at least 18 years who were trying to conceive and in relationships with an HIV-positive partner. Couples who were pregnant at enrolment or had been previously diagnosed as infertile were excluded. Participants received safer conception care by a nurse, including antiretroviral therapy (ART) for HIV-positive partners, pre-exposure prophylaxis (PrEP) for HIV-negative partners, counselling around timed condomless sex, or syringes for self-insemination. Primary outcomes were pregnancy incidence and HIV transmission to partners and infants. We estimated time to first pregnancy using Kaplan-Meier curves; pregnancy and HIV incidence were estimated as events per person-years of risk. FINDINGS: Between July 16, 2013, and April 5, 2017, 526 individuals (334 women and 192 men) from 334 partnerships enrolled. 162 (48%) of 334 couples were serodifferent, 149 (45%) were HIV-positive seroconcordant, and 23 (7%) were an HIV-positive woman and an unknown status male partner. At enrolment, 176 (61%) of 287 HIV-positive women and 60 (46%) of 131 HIV-positive men were virally suppressed (<50 copies per mL). Among the safer conception strategies, ART was initiated by 73 (91%) of 80 HIV-positive participants not on ART and PrEP was initiated by 28 (28%) of 101 HIV-negative participants. 2719 follow-up visits were completed, and 99 pregnancies were observed in 89 women. Pregnancy incidence was 41·2 per 100 person-years (95% CI 33·4-50·7); 25 (28%) of 89 pregnancies with a known outcome were miscarried or terminated because of risk to the mother. Pregnancy incidence was 79·0 per 100 person-years (95% CI 49·8-125·4) among HIV-negative women and 36·7 per 100 person-years (29·1-46·3) among HIV-positive women. At the time of pregnancy, viral suppression among women was high (68 [87%] of 78 women had viral loads of <50 copies per mL and 77 [99%] had viral loads of <1000 copies per mL). No horizontal or vertical HIV transmission events were observed. INTERPRETATION: Safer conception strategies empowered couples to safely conceive. Pregnancy incidence among service users was high. Integration of safer conception counselling could promote HIV prevention and linkage to care. FUNDING: US Agency for International Development; UJMT Consortium/Fogarty International Center, US National Institutes of Health (NIH); and Johns Hopkins University Center for AIDS Research (NIH).

Integrating safer conception services into primary care: providers' perspectives.

BACKGROUND: In 2012, South Africa adopted the Contraception and Fertility Planning guidelines to incorporate safer conception services into care for HIV-affected couples trying to conceive. These guidelines lacked clear implementation and training recommendations. The objective of this study was to investigate factors influencing integration of safer conception services in a clinical setting. METHODS: Twenty in-depth interviews were conducted between October-November 2017 with providers and staff at Witkoppen Clinic in Johannesburg, where the Sakh'umndeni safer conception demonstration project had enrolled patients from July 2013-July 2017. Semi-structured interview guides engaged providers on their perspectives following the Sakh'umndeni project and possible integration plans to inform the translation of the stand-alone Sakh'umndeni services into a routine service. A grounded theory approach was used to code interviews and an adaptation of the Atun et al. (2010) 'Integration of Targeted Interventions into Health Systems' conceptual framework was applied as an analysis tool. RESULTS: Five themes emerged: (1) The need for safer conception training; (2) The importance of messaging and demand generation; (3) A spectrum of views around the extent of integration of safer conception services; (4) Limitations of family planning services as an integration focal point; and (5) Benefits and challenges of a "couples-based" intervention. In-depth interviews suggested that counselors, as the first point of contact, should inform patients about safer conceptions services, followed by targeted reinforcement of safer conception messaging by all clinicians, and referral to more intensively trained safer conception providers. CONCLUSION: A safer conception counseling guide would facilitate consultations. While many providers felt that the services belonged in family planning, lack of HIV management skills, men and women trying to conceive within family planning may pose barriers.

The impact of community- versus clinic-based adherence clubs on loss from care and viral suppression for antiretroviral therapy patients: Findings from a pragmatic randomized controlled trial in South Africa.

BACKGROUND: Adherence clubs, where groups of 25-30 patients who are virally suppressed on antiretroviral therapy (ART) meet for counseling and medication pickup, represent an innovative model to retain patients in care and facilitate task-shifting. This intervention replaces traditional clinical care encounters with a 1-hour group session every 2-3 months, and can be organized at a clinic or a community venue. We performed a pragmatic randomized controlled trial to compare loss from club-based care between community- and clinic-based adherence clubs. METHODS AND FINDINGS: Patients on ART with undetectable viral load at Witkoppen Health and Welfare Centre in Johannesburg, South Africa, were randomized 1:1 to a clinic- or community-based adherence club. Clubs were held every other month. All participants received annual viral load monitoring and medical exam at the clinic. Participants were referred back to clinic-based standard care if they missed a club visit and did not pick up ART medications within 5 days, had 2 consecutive late ART medication pickups, developed a disqualifying (excluding) comorbidity, or had viral rebound. From February 12, 2014, to May 31, 2015, we randomized 775 eligible adults into 12 pairs of clubs-376 (49%) into clinic-based clubs and 399 (51%) into community-based clubs. Characteristics were similar by arm: 65% female, median age 38 years, and median CD4 count 506 cells/mm3. Overall, 47% (95% CI 44%-51%) experienced the primary outcome of loss from club-based care. Among community-based club participants, the cumulative proportion lost from club-based care was 52% (95% CI 47%-57%), compared to 43% (95% CI 38%-48%, p = 0.002) among clinic-based club participants. The risk of loss to club-based care was higher among participants assigned to community-based clubs than among those assigned to clinic-based clubs (adjusted hazard ratio 1.38, 95% CI 1.02-1.87, p = 0.032), after accounting for sex, age, nationality, time on ART, baseline CD4 count, and employment status. Among those who were lost from club-based care (n = 367), the most common reason was missing a club visit and the associated ART medication pickup entirely (54%, 95% CI 49%-59%), and was similar by arm (p = 0.086). Development of an excluding comorbidity occurred in 3% overall of those lost from club-based care, and was not different by arm (p = 0.816); no deaths occurred in either arm during club-based care. Viral rebound occurred in 13% of those lost from community club-based care and 21% of those lost from clinic-based care (p = 0.051). In post hoc secondary analysis, among those referred to standard care, 72% (95% CI 68%-77%) reengaged in clinic-based care within 90 days of their club-based care discontinuation date. The main limitations of the trial are the lack of a comparison group receiving routine clinic-based standard care and the potential limited generalizability due to the single-clinic setting. CONCLUSIONS: These findings demonstrate that overall loss from an adherence club intervention was high in this setting and that, importantly, it was worse in community-based adherence clubs compared to those based at the clinic. We urge caution in assuming that the effectiveness of clinic-based interventions will carry over to community settings, without a better understanding of patient-level factors associated with successful retention in care. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR201602001460157).

Infant feeding by South African mothers living with HIV: implications for future training of health care workers and the need for consistent counseling.

Background: Since 2010, the World Health Organization recommends lifelong antiretroviral treatment for all women living with HIV, and exclusive breastfeeding for six-months followed by breastfeeding until 24-months for all HIV positive mothers. Nevertheless, many mothers living with HIV do not initiate breastfeeding or stop prematurely, and many countries are still in the process of updating their national infant feeding guidelines to align with World Health Organization recommendations. We sought to understand uptake of breastfeeding and factors that influence decision-making regarding infant feeding in women living with and without HIV who receive ante- and postnatal care at a primary healthcare setting. Methods: Programmatic data on infant feeding intentions and practices among women attending an ante-and postnatal clinic service at a primary care clinic in Johannesburg, South Africa were summarized using descriptive statistics. Qualitative interviews were conducted with 12 healthcare providers, 12 women living with HIV who were breastfeeding and 10 who were formula feeding. Interviews were analyzed using a content analysis approach. Results: Pregnant women living with HIV were less likely to express an intent to breastfeed (71% vs 99%). During the first 6 months postpartum, mothers living with HIV were also less likely to exclusively breastfeed compared to HIV-negative mothers. Mixed messages during infant feeding counselling, social and economic factors, and fear of HIV transmission influenced women's choices to initiate and continue breastfeeding. Conclusions: As infant feeding guidelines for women living with HIV have evolved rapidly in the past 10 years, uniform messages on the low risk of mother-to-child transmission of HIV associated with breastfeeding while on ART and on introduction of complementary foods after 6 months of age are needed.

Subfertility among HIV-affected couples in a safer conception cohort in South Africa.

BACKGROUND: Subfertility among couples affected by HIV has an impact on the well-being of couples who desire to have children and may prolong HIV exposure. Subfertility in the antiretroviral therapy era and its determinants have not yet been well characterized. OBJECTIVE: The objective of the study was to investigate the burden and determinants of subfertility among HIV-affected couples seeking safer conception services in South Africa. STUDY DESIGN: Nonpregnant women and male partners in HIV seroconcordant or HIV discordant relationships desiring a child were enrolled in the Sakh'umndeni safer conception cohort at Witkoppen Clinic in Johannesburg between July 2013 and April 2017. Clients were followed up prospectively through pregnancy (if they conceived) or until 6 months of attempted conception, after which they were referred for infertility services. Subfertility was defined as not having conceived within 6 months of attempted conception. Robust Poisson regression was used to assess the association between baseline characteristics and subfertility outcomes; inverse probability weighting was used to account for missing data from women lost to safer conception care before 6 months of attempted conception. RESULTS: Among 334 couples enrolled, 65% experienced subfertility (inverse probability weighting weighted, 95% confidence interval, 0.59-0.73), of which 33% were primary subfertility and 67% secondary subfertility. Compared with HIV-negative women, HIV-positive women not on antiretroviral therapy had a 2-fold increased risk of subfertility (weighted and adjusted risk ratio, 2.00; 95% confidence interval, 1.19-3.34). Infertility risk was attenuated in women on antiretroviral therapy but remained elevated, even after ≥2 years on antiretroviral therapy (weighted and adjusted risk ratio, 1.63; 95% confidence interval, 0.98-2.69). Other factors associated with subfertility were female age (weighted and adjusted risk ratio, 1.03, 95% confidence interval, 1.01-1.05 per year), male HIV-positive status (weighted and adjusted risk ratio, 1.31; 95% confidence interval, 1.02-1.68), male smoking (weighted and adjusted risk ratio, 1.29; 95% confidence interval, 1.05-1.60), and trying to conceive for ≥1 year (weighted and adjusted risk ratio, 1.38; 95% confidence interval, 1.13-1.68). CONCLUSION: Two in 3 HIV-affected couples experienced subfertility. HIV-positive women were at increased risk of subfertility, even when on antiretroviral therapy. Both male and female HIV status were associated with subfertility. Subfertility is an underrecognized reproductive health problem in resource-limited settings and may contribute to prolonged HIV exposure and transmission within couples. Low-cost approaches for screening and treating subfertility in this population are needed.

Health system barriers to implementation of TB preventive strategies in South African primary care facilities.

BACKGROUND: Isoniazid preventive therapy (IPT) is a key component of TB/HIV control, but few countries achieve high IPT coverage. METHODS: Using a behavioural COM-B design approach, the intervention consisted of a training on IPT guidelines and tuberculin skin testing (TST), identification of the optimal IPT implementation strategy by the health care workers (HCWs) of 3 primary care clinics, and a 2-month mentoring period. Using routine register data, TST and IPT uptake was determined 3 months before and 5 months after the intervention. Records were reviewed to identify factors associated with IPT initiation and HCW fidelity to the guidelines. A survey among HCWs was conducted to determine barriers to IPT. RESULTS: Two clinics implemented TST-guided IPT for all clients receiving HIV care, one clinic decided against use of TST. According to routine register data, the proportion of clients initiating IPT increased substantially at the clinic not opting for TST (6% vs 36%), but minimally (34% vs 37% and 0.7% vs 3%) in the two other clinics. TST uptake did not increase (0 vs 0% and 0.5%). In addition to poor IPT uptake, HCW fidelity to investigation for TB and timing of IPT initiation was poor, with only 68% of symptomatic patients investigated and IPT initiation delayed to a median of 374 days post-ART initiation. In multivariate analysis, pregnancy (aOR 18.62, 95% CI 6.99-53.46), recent HIV diagnosis (aOR 3.65, 95% CI 1.73-7.41), being on ART (aOR 9.44, 95% CI 3.05-36.17), and CD4 <500 cells/mm3 (aOR 2.19, 95% CI 1.22-4.18) were associated with IPT initiation. Time needed to perform a TST, motivating patients to return for TST reading, and low IPT patient awareness were the main barriers to IPT implementation. CONCLUSION: Despite using a behavioural intervention framework including training and participatory development of the clinic IPT strategy, HCW fidelity to the guidelines was poor, resulting in low TST coverage and low IPT uptake under primary care conditions. To achieve the benefits of IPT, health system level approaches including TST-free guidelines and sensitization are needed.

Mental health in South African adolescents living with HIV.

We examined the prevalence of mental health conditions, social support, and associated factors among adolescents living with HIV. We conducted a cross-sectional analysis with adolescents (ages 9-19) attending a primary care clinic in Johannesburg, South Africa. We analyzed the results of four self-report tools: Children's Depression Inventory-Short, Revised Manifest Anxiety Scale, Child Post-Traumatic Stress Disorder (PTSD) Checklist, and a modified version of the Medical Outcomes Study Social Support Scale. We used robust Poisson regression to quantify the association between social support and mental health. Among 278 adolescents, the majority were perinatally infected with HIV (92%), and had at least one deceased parent (59%). Depression symptom threshold scores were found among 8% of adolescents, and 7% screened positive for symptoms of anxiety. Few (1%) met the criteria for PTSD. Overall, 12% of adolescents screened positive for symptoms of depression, anxiety or PTSD. Older adolescents reported less social support than younger adolescents. Adolescents were less likely to have mental health symptoms if they had higher measures of social support (adjusted Prevalence Ratio 0.38, 95% CI 0.20-0.73). Attention should be paid to social support for adolescents living with HIV as this may play an important role in their mental health.

Diagnostic strategies for childhood tuberculosis in the context of primary care in a high burden setting: the value of alternative sampling methods.

Background: Hospital studies have demonstrated the usefulness of alternative sampling strategies to expectorated sputum and new diagnostics for the diagnosis of childhood tuberculosis (TB) but there is limited evidence of how these approaches work in the primary-care setting. Aim: To assess the feasibility and yield of a variety of sample types and diagnostic tests for childhood TB at a primary-care clinic. Methods: A prospective cohort of children (<10 years) with signs and symptoms of TB was enrolled at a primary-care clinic in Johannesburg, South Africa. Tuberculin skin testing (TST) and chest X-ray (CXR) were performed in all. In those unable to expectorate, one induced sputum (IS), one ambulatory gastric aspirate (GA) and two nasopharyngeal aspirates (NPA) were collected. Stool was collected from all. Samples were processed for smear microscopy, liquid culture and Xpert MTB/RIF. The Determine TB LAM Ag (LAM) test was used for HIV-positive children. Results: From July 2013-December 2014, 119 children were enrolled, 21 (18%) of whom were HIV-positive. TST was positive in 25/105 (24%) and 70/116 (70%) had a positive CXR. Four (3%) had confirmed TB, 101 (85%) unconfirmed TB and 15 (13%) unlikely TB. Of the 469 samples collected, smear microscopy was positive in none, Xpert was positive in four (<1%) and culture was positive in two (<1%). Three of 11 (27%) HIV-positive patients were positive by LAM. Treatment was commenced in 48/119 (40%). Conclusions: At primary-care, alternative sampling strategies proved feasible but resulted in a low diagnostic yield. Extensive efforts to bacteriologically diagnose children did not contribute to clinical management.

"I will leave the baby with my mother": Long-distance travel and follow-up care among HIV-positive pregnant and postpartum women in South Africa.

INTRODUCTION: It is common in urban African settings for postpartum women to temporarily return to family in distant settings. We sought to explore mobility among peripartum HIV-positive women to understand the timing and motivation of travel, particularly vis-à-vis delivery, and how it may affect healthcare access. METHODS: Using the same mobility measurements within three different studies, we examined long-distance travel of mother and infant before and after delivery in three diverse clinics within greater Johannesburg, South Africa (n = 150). Participants were interviewed prior to delivery at two sites (n = 125) and after delivery at one (n = 25). Quantitative and qualitative results are reported. RESULTS: Among 150 women, median age was 29 years (IQR: 26 to 34) and 36.3% were employed. Overall, 76.7% of the participants were born in South Africa: 32.7% in Gauteng Province (Johannesburg area) and 44.0% in other South African provinces, but birthplace varied greatly by site. Almost half (44.0%) planned to travel around delivery; nearly all after delivery. Median duration of stay was 30 days (IQR: 24 to 90) overall, but varied from 60 days at two sites to just 7 days at another. Participants discussed travel to eight of South Africa's nine provinces and four countries. Travel most frequently was to visit family, typically to receive help with the new baby. Nearly all the employed participants planned to return to work in Johannesburg after delivery, sometimes leaving the infant in the care of family outside of Johannesburg. All expressed their intent to continue HIV care for themselves and their infant, but few planned to seek care at the destination site, and care for the infant was emphasized over care for the mother. CONCLUSIONS: We identified frequent travel in the peripartum period with substantial differences in travel patterns by site. Participants more frequently discussed seeking care for the infant than for themselves. HIV-exposed children often were left in the care of family members in distant areas. Our results show the frequent mobility of women and infants in the peripartum period. This underscores the challenge of ensuring a continuity of HIV care in a fragmented healthcare system that is not adapted for a mobile population.

Cohort profile: the Right to Care Clinical HIV Cohort, South Africa.

PURPOSE: The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. PARTICIPANTS: The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3-6 months for clinical and laboratory monitoring. FINDINGS TO DATE: Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. FUTURE PLANS: Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa.