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.

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.

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).

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.

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.

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.

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.

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.

"I don't know if this is right but this is what I'm offering": healthcare provider knowledge, practice, and attitudes towards safer conception for HIV-affected couples in the context of Southern African guidelines.

The 2011 guidelines for safer conception for HIV-affected individuals and couples were adopted by the South African Department of Health in December 2012. We assessed implementation gaps and facilitators and barriers to delivering safer conception services through examining patient and healthcare provider (HCP) experiences. At Witkoppen Health and Welfare Centre, a primary care clinic in Johannesburg, we conducted in-depth interviews (IDIs) with nine HCPs (doctors, nurses, and counselors) and IDIs and focus group discussions with 42 HIV-affected men and women interested in having a child. Data were analyzed using a grounded theory approach. HCPs were supportive of fertility intentions of HIV-affected couples and demonstrated some knowledge of safer conception methods, especially ART initiation to suppress viral load in infected partners. Unfortunately, HCPs did not follow the key recommendation that HCPs initiate conversations on fertility intentions with HIV-affected men and women. Providers and clients reported that conversations about conception only occur when client-initiated, placing the onus on HIV-affected individuals. Important barriers underlying this were the misconception held by some HCPs that uninfected partners in serodiscordant partnerships are "latently" infected and the desire by most HCPs to protect or control knowledge around fertility and safer conception methods out of concern over what clients will do with this knowledge before they are virally suppressed or ready to conceive. Almost all participants who had conceived or attempted conception did so without safer conception methods knowledge. HCP concern over conception readiness, perception of what clients will do with safer conception knowledge, and gaps in safer conception knowledge prevent HCPs from initiating conversations with HIV-affected patients on the issue of childbearing. Examining these findings in the context of existing South African guidelines illuminates areas that need to be addressed to facilitate implementation of the guidelines.

Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study.

BACKGROUND: South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. METHODS: Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI RESULTS: The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0-14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01-1.05), male gender (OR = 2.70, 95 % CI = 1.55-4.70), marital status (OR = 2.00, 95 % CI = 1.31-3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04-4.31). CONCLUSIONS: The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty.

Xpert MTB/RIF as a measure of sputum bacillary burden. Variation by HIV status and immunosuppression.

RATIONALE: Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited. OBJECTIVES: Examine the impact of HIV status and level of immunosuppression on the distribution of mean cycle threshold values, and the correlation of cycle threshold values and smear microscopy grade with time to culture positivity. METHODS: Paired sputum samples from 2,406 individuals with suspected pulmonary tuberculosis in South Africa were tested by Xpert MTB/RIF, concentrated smear microscopy, and liquid culture to quantify bacterial burden using cycle threshold values, smear grading, and time to culture positivity. MEASUREMENTS AND MAIN RESULTS: Cycle threshold values were lower in HIV-uninfected versus HIV-infected individuals (22.9 vs. 26.6; P < 0.001). Among HIV-infected, CD4 count was an independent predictor of cycle threshold value, with an average increase of 1.50 cycles for CD4 count greater than or equal to 200 (P 0.071) and 3.66 cycles for CD4 count less than 200 (P < 0.001) compared with HIV-uninfected individuals. Correlation between cycle threshold value and time to culture positivity was similar to that between smear status and time to culture positivity (both Spearman ρ 0.58). The strength of correlation between measures decreased as the level of immunosuppression increased. A cycle threshold value cutoff of 28 had good predictive value for smear positivity. CONCLUSIONS: We observed decreasing bacillary burden with increasing level of immunosuppression as measured by Xpert MTB/RIF cycle threshold values. A cycle threshold value of 28 can be used as a measure of bacterial burden and smear status in a high HIV burden setting.

Acceptability and Feasibility of a Mobile Phone-Based Case Management Intervention to Retain Mothers and Infants from an Option B+ Program in Postpartum HIV Care.

The objective of this study was to assess the acceptability and feasibility of a cell phone based case manager intervention targeting HIV-infected pregnant women on highly-active antiretroviral therapy (HAART). Pregnant women ≥36 weeks gestation attending antenatal care and receiving HAART through the Option B+ program at a primary care clinic in South Africa were enrolled into a prospective pilot intervention to receive text messages and telephone calls from a case manager through 6 weeks postpartum. Acceptability and feasibility of the intervention were assessed along with infant HIV testing rates and 10-week and 12-month postpartum maternal retention in care. Retention outcomes were compared to women of similar eligibility receiving care prior to the intervention. Fifty women were enrolled into the pilot from May to July 2013. Most (70%) were HAART-naive at time of conception and started HAART during antenatal care. During the intervention, the case manager sent 482 text messages and completed 202 telephone calls, for a median of 10 text messages and 4 calls/woman. Ninety-six percent completed the postpartum interview and 47/48 (98%) endorsed the utility of the intervention. Engagement in 10-week postpartum maternal HIV care was >90% in the pre-intervention (n = 50) and intervention (n = 50) periods; by 12-months retention fell to 72% and was the same across periods. More infants received HIV-testing by 10-weeks in the intervention period as compared to pre-intervention (90.0 vs. 63.3%, p < 0.01). Maternal support through a cell phone based case manager approach was highly acceptable among South African HIV infected women on HAART and feasible, warranting further assessment of effectiveness.

Impact of systematic HIV testing on case finding and retention in care at a primary care clinic in South Africa.

OBJECTIVE: Systematic, opt-out HIV counselling and testing (HCT) may diagnose individuals at lower levels of immunodeficiency but may impact loss to follow-up (LTFU) if healthier people are less motivated to engage and remain in HIV care. We explored LTFU and patient clinical outcomes under two different HIV testing strategies. METHODS: We compared patient characteristics and retention in care between adults newly diagnosed with HIV by either voluntary counselling and testing (VCT) plus targeted provider-initiated counselling and testing (PITC) or systematic HCT at a primary care clinic in Johannesburg, South Africa. RESULTS: One thousand one hundred and forty-four adults were newly diagnosed by VCT/PITC and 1124 by systematic HCT. Two-thirds of diagnoses were in women. Median CD4 count at HIV diagnosis (251 vs. 264 cells/µl, P = 0.19) and proportion of individuals eligible for antiretroviral therapy (ART) (67.2% vs. 66.7%, P = 0.80) did not differ by HCT strategy. Within 1 year of HIV diagnosis, half were LTFU: 50.5% under VCT/PITC and 49.6% under systematic HCT (P = 0.64). The overall hazard of LTFU was not affected by testing policy (aHR 0.98, 95%CI: 0.87-1.10). Independent of HCT strategy, males, younger adults and those ineligible for ART were at higher risk of LTFU. CONCLUSIONS: Implementation of systematic HCT did not increase baseline CD4 count. Overall retention in the first year after HIV diagnosis was low (37.9%), especially among those ineligible for ART, but did not differ by testing strategy. Expansion of HIV testing should coincide with effective strategies to increase retention in care, especially among those not yet eligible for ART at initial diagnosis.

Loss to follow-up before and after delivery among women testing HIV positive during pregnancy in Johannesburg, South Africa.

OBJECTIVE: HIV-positive pregnant women are at heightened risk of becoming lost to follow-up (LTFU) from HIV care. We examined LTFU before and after delivery among pregnant women newly diagnosed with HIV. METHODS: Observational cohort study of all pregnant women ≥18 years (N = 300) testing HIV positive for the first time at their first ANC visit between January and June 2010, at a primary healthcare clinic in Johannesburg, South Africa. Women (n = 27) whose delivery date could not be determined were excluded. RESULTS: Median (IQR) gestation at HIV testing was 26 weeks (21-30). Ninety-eight per cent received AZT prophylaxis, usually started at the first ANC visit. Of 139 (51.3%) patients who were ART eligible, 66.9% (95% CI 58.8-74.3%) initiated ART prior to delivery; median (IQR) ART duration pre-delivery was 9.5 weeks (5.1-14.2). Among ART-eligible patients, 40.5% (32.3-49.0%) were cumulatively retained through 6 months on ART. Of those ART-ineligible patients at HIV testing, only 22.6% (95% CI 15.9-30.6%) completed CD4 staging and returned for a repeat CD4 test after delivery. LTFU (≥1 month late for last scheduled visit) before delivery was 20.5% (95% CI 16.0-25.6%) and, among those still in care, 47.9% (95% CI 41.2-54.6%) within 6 months after delivery. Overall, 57.5% (95% CI 51.6-63.3%) were lost between HIV testing and 6 months post-delivery. CONCLUSIONS: Our findings highlight the challenge of continuity of care among HIV-positive pregnant women attending antenatal services, particularly those ineligible for ART.

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.

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.

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.

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.