Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Treatment initiation among tuberculosis patients: the role of short message service (SMS) technology and Ward-based outreach teams (WBOTs).

BACKGROUND: In South Africa, tuberculosis (TB) is a public health problem with treatment initiation failure rates varying between 14.9 and 25%. Lack of proper provider/patient communication on next steps after testing, not being aware that results are ready; and other competing priorities are some of the reasons for this failure. We aimed to assess the effectiveness of Short Message Service (SMS) technology and ward-based outreach teams (WBOTs) in improving TB treatment initiation. A 3-arm randomized controlled trial (Standard of care-SOC, SMS technology or WBOTs) was conducted between September 2018 and April 2020. Newly diagnosed TB patients randomly allocated to SMS and WBOTs groups were sent reminder messages (text message or paper slip respectively) that results were ready. Due to unforeseen challenges (financial and impact of the COVID 19 pandemic), implementation was only in two of the eight clinics planned. RESULTS: 314 TB patients were assigned to one of three groups (SOC = 104, WBOTs = 105, and SMS = 105). Chi-square tests were used to compare proportions starting treatment (primary outcome). More patients in the SMS group (92/105; 88%) initiated treatment than in the SOC group (81/104; 78%), although this difference did not reach statistical significance (P = 0.062). The time to treatment initiation was significantly shorter in the SMS group than in the SOC group (P < 0.001). The proportions of patients initiated on treatment in the WBOTs group (45/62; 73%) and in the SOC group (44/61; 72%) were similar (P = 0.956). The times to treatment initiation for these two groups were also similar. The 3 group analysis yielded similar proportions initiated on treatment (P = 0.048 for SMS/SOC comparison and P = 0.956 for WBOTs/SOC comparison) but analysis of times to treatment initiation yielded some variations. CONCLUSION: Reminder SMS messages sent to newly diagnosed TB patients improved the time to treatment initiation. Further research is required to show effect of the WBOTs intervention. TRIAL REGISTRATION: Retrospectively registered with the Pan African Clinical Trial Registry ( PACTR202101914895981 ). The trial was registered with the Pan African Clinical Trial Registry on 25 January, 2021 (ref: PACTR202101914895981 ; https://pactr.samrc.ac.za ). The registration was retrospective due to an oversight. Nevertheless, the protocol details outlined in our ethics application were strictly adhered to.

Effects of HIV voluntary medical male circumcision programs on sexually transmitted infections.

PURPOSE OF REVIEW: Evidence of the protective effect of voluntary medical male circumcision (VMMC) against HIV is well established. However, evidence of the protective effect of VMMC against other sexually transmitted infections (STIs) has been inconsistent or scarce across different populations and settings. This review summarizes the current evidence on the effect of VMMC for HIV prevention on acquisition and transmission of other STIs in heterosexual men, women, and men who have sex with men (MSM). RECENT FINDINGS: Recent findings continue to strongly support the protective effect of male medical circumcision against acquisition and transmission of herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV) and syphilis infections in heterosexual men and women, and bacterial vaginosis and trichomoniasis in women. There is emerging evidence on the protective effect of VMMC against acquisition of hepatitis B and Mycoplasma genitalium infections in heterosexual men, and HSV-2, HPV, and syphilis in MSM. SUMMARY: Evidence on the protective effect of VMMC against acquisition and transmission of common STIs is available for heterosexual men and women but more evidence is required for MSM. This review supports policy recommendations for the protective benefits of VMMC against STIs.

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus-co-infected patients in Myanmar.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.

Trends, prevalence and factors associated with hypertension and diabetes among South African adults living with HIV, 2005-2017.

BACKGROUND: Many people are now living longer with HIV due to access to antiretroviral treatment. In turn, there has been an increase in the burden of hypertension and diabetes. The paucity of data on the burden of hypertension and diabetes in adults living with HIV in South Africa is a public health concern. The paper aimed to describe the prevalence and factors associated with hypertension and diabetes among adults living with HIV (ALHIV). METHODS: This was a secondary data analysis of the population based on the South African National HIV Prevalence, Incidence, Behaviour and Communication surveys for 2005, 2008 and 2017. Descriptive statistics were used to summarise the characteristics of the study sample. Bivariate and multivariate logistic regression analyses were used to determine factors associated with hypertension and diabetes. RESULTS: The total study population of ALHIV aged 25 years and older was 978, 1023 and 2483 for 2005, 2008 and 2017. The prevalence of hypertension showed an increasing trend at 11.8% in 2005, 9.5% in 2008 and 14.3% in 2017. The prevalence of diabetes was 3.3% in 2005, 2.8% in 2008 and 3.2% in 2017. Increased odds of hypertension among adults living with HIV were consistently associated with being female and the age group 45 years older across all the survey years, including pensioners and the sick, living in urban areas, high risk of hazardous alcohol consumption, diabetes and heart disease. Increased odds of diabetes were consistently associated with hypertension across all the survey years, including age group 45 years and older, and poor health. While having a secondary level of education and above was protective against diabetes. CONCLUSION: The study showed that the prevalence of hypertension is high and has increased over time among adults living with HIV while the prevalence of diabetes has remained constant. Findings identified factors consistently associated with the prevalence of both diseases overtime, including contemporary risk factors that should be targeted in the integrated management of chronic disease and HIV care model.

Factors associated with an interruption in treatment of people living with HIV in USAID-supported states in Nigeria: a retrospective study from 2000-2020.

BACKGROUND: Patient interruption of antiretroviral therapy (ART) continues to limit HIV programs' progress toward epidemic control. Multiple factors have been associated with client interruption in treatment (IIT)- including age, gender, CD4 count, and education level. In this paper, we explore the factors associated with IIT in people living with HIV (PLHIV) in United States Agency for International Development (USAID)-supported facilities under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. METHODS: We conducted cross-sectional analyses on data obtained from Nigeria's National Data Repository (NDR), representing a summarized record of 573 630 ART clients that received care at 484 PEPFAR/USAID-supported facilities in 16 states from 2000-2020. IIT was defined as no clinical contact for 28 days or more after the last expected clinical contact. Univariate and multivariate logistic regression models were computed to explore the factors associated with IIT. The variables included in the analysis were sex, age group, zone, facility level, regimen line, multi-month dispensing (MMD), and viral load category. RESULTS: Of the 573 630 clients analysed in this study, 32% have been recorded as having interrupted treatment. Of the clients investigated, 66% were female (32% had interrupted treatment), 39% were aged 25-34 at their last ART pick-up date (with 32% of them interrupted treatment), 59% received care at secondary level facilities (37% interrupted treatment) and 38% were last receiving between three- to five-month MMD (with 10% of these interrupted treatment). Those less likely to interrupt ART were males (aOR = 0.91), clients on six-month MMD (aOR = 0.01), adults on 2nd line regimen (aOR = 0.09), and paediatrics on salvage regimen (aOR = 0.02). Clients most likely to interrupt ART were located in the South West Zone (aOR = 1.99), received treatment at a tertiary level (aOR = 12.34) or secondary level facilities (aOR = 4.01), and had no viral load (VL) on record (aOR =10.02). Age group was not significantly associated with IIT. CONCLUSIONS: Sex, zone, facility level, regimen line, MMD, and VL were significantly associated with IIT. MMD of three months and longer (especially six months) had better retention on ART than those on shorter MMD. Not having a VL on record was associated with a considerable risk of IIT.

Social franchising of community-based HIV counselling and testing services to increase HIV testing and linkage to care in Tshwane, South Africa: study protocol for a non-randomised implementation trial.

BACKGROUND: Meeting the ambitious UN 90-90-90 HIV testing, treatment and viral load suppression targets requires innovative strategies and approaches in Sub-Saharan Africa. To date no known interventions have been tested with community health workers (counsellors) as social franchisees or owner-managed businesses in Community-based HIV counselling and testing (CBCT) work. The aim of this methods paper is to describe a Social franchise (SF) CBCT implementation trial to increase HIV testing and linkage to care for individuals at community levels in comparison with an existing CBCT programme methods. METHODS/DESIGN: This is a two arm non-randomised community implementation trial with a once off round of post-test follow-up per HIV positive participant to assess linkage to care in low income communities. The intervention arm is a social franchise CBCT in which unemployed, self-employed or employed community members are recruited, contracted and incentivised to test at least 100 people per month, identifying at least 5 HIV positive tests and linking to care at least 4 of them. Social franchisees receive approximately $3.20 per HIV test and $8 per client linked to care. In the control arm, full-time employed HIV counsellors conduct CBCT on a fixed monthly salary. Primary study outcomes are HIV testing uptake rate, HIV positivity, Linkage to care and treatment rate and average counsellors' remuneration cost. Data collection will be conducted using both paper-based and electronic data applications by CBCT or SF counsellors. Data analysis will compare proportions of HIV testing, positivity, linkage to HIV care and treatment rates and counsellors' cost in the two study arms. DISCUSSION: The study will provide important insight into whether the SF-delivered CBCT programme increases testing coverage and linkage to care as well as reducing CBCT cost per HIV test and per HIV positive person linked to care. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR201809873079121. The trial was retrospectively registered on 11 September 2018.

Initial loss to follow up of tuberculosis patients in South Africa: perspectives of program managers.

BACKGROUND: Tuberculosis (TB) remains a serious public health problem in South Africa. Initial loss to follow up (LTFU) rates among TB patients are high, varying between 14.9 and 22.5%. From the perspective of patients, documented reasons for this include poor communication between patient and staff after testing, not being aware that results are ready and other competing priorities such as preference to go to work as opposed to seeking healthcare. Ward-based Outreach Teams (WBOTs) routinely conduct home visits to ensure adherence to medication for various conditions including TB. We explored reasons for TB initial loss to follow up from the perspectives of TB program managers and WBOT program managers, with a focus on the WBOT's (potential) role in reducing initial LTFU, in particular. METHODS: Key informant interviews with five WBOT program managers and four TB program managers were conducted. The interviews were audio-recorded, then transcribed and exported to NVivo 11 software for coding. A hybrid analytic approach consisting of both inductive and deductive coding was used to identify themes. RESULTS: The age of the nine managers ranged between 28 and 52 years old, of which two were male. They had been in their current position for between 2 to 12 years. Prior to treatment initiation, WBOTs screen household members for TB and refer them for TB testing if need be, but integration of the two programs is emphasized only after TB treatment has been initiated. Counseling of patients testing for TB is not guaranteed due to frequent staff rotations and staff shortages. Participants reported that possible dissatisfaction with services as well as stigma associated with the TB diagnosis could explain loss to follow up prior to treatment initiation. CONCLUSION: Program managers view health system related factors such as staff rotations, poor communication with patients and lack of counseling as contributing to the problem of initial LTFU among TB patients. The integration of the WBOT and TB programs is limited to referring suspected cases for testing and patients already on treatment.

Challenges with seeking HIV care services: perspectives of older adults infected with HIV in western Kenya.

BACKGROUND: While younger adults (15-49 years) form the majority of the population living with HIV, older adults (≥50 years) infected with HIV face multiple challenges related to the aging process and HIV. We explored the experiences of older persons infected with HIV at the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya to understand the challenges faced when seeking HIV care services. METHODS: Between November 2016 and April 2017, a total of 57 adults aged 50 years and above were recruited from two AMPATH facilities - one rural and one urban facility. A total of 25 in-depth interviews and four focus group discussions were conducted, audio-recorded, transcribed and thematic analysis performed. RESULTS: Study participants raised unique challenges with seeking HIV care that include visits to multiple healthcare providers to manage HIV and comorbidities and as a result impact on their adherence to medication and clinical visits. Challenges with inadequate quality of facilities and poor patient-provider communication were also raised. Participants' preference for matched gender and older age for care providers that serve older patients were identified. CONCLUSION: Results indicate multiple challenges faced by older adults that need attention in ensuring continuous engagement in HIV care. Targeted HIV care for older adults would, therefore, significantly improve their access to and experience of HIV care. Of key importance is the integration of other chronic diseases into HIV care and employing staff that matches the needs of older adults.

Talking about sex in pregnancy: reflections from the field in urban South Africa.

Qualitative research with close engagement in the field allows researchers and participants to build relationships and establish trust, enabling researchers to collect meaningful and sensitive information. Drawing on findings from a study conducted in an urban setting in South Africa, we discuss the challenges faced when interviewing pregnant women with HIV infection, retaining them in the study, and extending the study to include their partners. We discuss the dynamics of pregnancy and draw lessons from interviews concerned with personal, sensitive issues. The study on which we draw was conducted in Johannesburg, South Africa, and was nested in a larger prospective cohort study of women and their infants, which in turn was part of a case control study. Sensitive topics are difficult and complex, but to ignore these and stay in safe territory is to ignore some of the most pressing questions of our time. It is important that those who conduct interviews are well trained and able to engage empathetically with participants, and that some form of counselling is available for both participants and researchers.

The effects of a lipid-based nutrient supplement and antiretroviral therapy in a randomized controlled trial on iron, copper, and zinc in milk from HIV-infected Malawian mothers and associations with maternal and infant biomarkers.

We evaluated effects of antiretroviral (ARV) therapy and lipid-based nutrient supplements (LNSs) on iron, copper, and zinc in milk of exclusively breastfeeding HIV-infected Malawian mothers and their correlations with maternal and infant biomarkers. Human milk and blood at 2, 6, and 24 weeks post-partum and blood during pregnancy (≤30 weeks gestation) were collected from 535 mothers/infant-pairs in the Breastfeeding, Antiretrovirals, and Nutrition study. The participants received ARV, LNS, ARV and LNS, or no intervention from 0 to 28 weeks post-partum. ARVs negatively affected copper and zinc milk concentrations, but only at 2 weeks, whereas LNS had no effect. Among all treatment groups, approximately 80-90% of copper and zinc and <50% of iron concentrations met the current adequate intake for infants at 2 weeks and only 1-19% at 24 weeks. Pregnancy haemoglobin was negatively correlated with milk iron at 2 and 6 weeks (r = -.18, p < .02 for both). The associations of the milk minerals with each other were the strongest correlations observed (r = .11-.47, p < .05 for all); none were found with infant biomarkers. At 2 weeks, moderately anaemic women produced milk higher in iron when ferritin was higher or TfR lower. At 6 weeks, higher maternal α-1-acid glycoprotein and C-reactive protein were associated with higher milk minerals in mildly anaemic women. Infant TfR was lower when milk mineral concentrations were higher at 6 weeks and when mothers were moderately anaemic during pregnancy. ARV affects copper and zinc milk concentrations in early lactation, and maternal haemoglobin during pregnancy and lactation could influence the association between milk minerals and maternal and infant iron status and biomarkers of inflammation.

Co-trimoxazole Prophylaxis, Asymptomatic Malaria Parasitemia, and Infectious Morbidity in Human Immunodeficiency Virus-Exposed, Uninfected Infants in Malawi: The BAN Study.

Background: Human immunodeficiency virus (HIV)-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear. Methods: We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of (1) CPT and (2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6 to 36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEIs) at 8 weeks of age (n = 1984) were included when CPT was the exposure. A subset of HEIs (n = 471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity. Results: CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio [HR], 0.64 [95% confidence interval {CI}, .60-.69]) and a 41% reduction in diarrheal morbidity (HR, 0.59 [95% CI, .54-.65]). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR, 1.40 [95% CI, 1.13-1.74]) and a 50% increase in diarrheal morbidity (HR, 1.50 [95% CI, 1.09-2.06]), after adjusting for CPT. Conclusions: CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings.

Effect of Postnatal HIV Treatment on Clinical Mastitis and Breast Inflammation in HIV-Infected Breast-feeding Women.

BACKGROUND: The relationship between mastitis and antiretroviral therapy among HIV-positive, breast-feeding women is unclear. METHODS: In the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, conducted in Lilongwe, Malawi, 2369 mother-infant pairs were randomized to a nutritional supplement group and to one of three treatment groups: maternal antiretroviral therapy (ART), infant nevirapine (NVP) or standard of care for 24 weeks of exclusive breast-feeding and 4 weeks of weaning. Among 1472 HIV-infected women who delivered live infants between 2004 and 2007, we estimated cumulative incidence functions and sub-distribution hazard ratios (HR) of mastitis or breast inflammation comparing women in maternal ART (n = 487) or infant nevirapine (n = 492) groups to the standard of care (n = 493). Nutritional supplement groups (743 took, 729 did not) were also compared. RESULTS: Through 28-weeks post-partum, 102 of 1472 women experienced at least one occurrence of mastitis or breast inflammation. The 28-week risk was higher for maternal ART (risk difference (RD) 4.5, 95% confidence interval (CI) 0.9, 8.1) and infant NVP (RD 3.6, 95% CI 0.3, 6.9) compared to standard of care. The hazard of late-appearing mastitis or breast inflammation (from week 5-28) was also higher for maternal ART (HR 6.7, 95% CI 2.0, 22.6) and infant NVP (HR 5.1, 95% CI 1.5, 17. 5) compared to the standard of care. CONCLUSIONS: Mastitis or breast inflammation while breast-feeding is a possible side effect for women taking prophylactic ART and women whose infants take NVP, warranting additional research in the context of postnatal HIV transmission.

Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed, uninfected infants.

BACKGROUND: Cotrimoxazole preventive therapy (CPT) is recommended for all human immunodeficiency virus (HIV)-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown. METHODS: We conducted an observational cohort study using data and dried blood spots (DBSs) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence 1 year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBSs at 12, 24, and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections. RESULTS: CPT was associated with a 70% (95% confidence interval, 53%-81%) relative reduction in the risk of asymptomatic infection between 6 and 36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics. CONCLUSIONS: CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits.

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women.

BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Reducing lost to follow-up in a large clinical trial of prevention of mother-to-child transmission of HIV: the Breastfeeding, Antiretrovirals and Nutrition study experience.

BACKGROUND/AIMS: Retaining patients in prevention of mother-to-child transmission of HIV studies can be challenging in resource-limited settings, where high lost to follow-up rates have been reported. In this article, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition study and analyze factors associated with lost to follow-up in the study. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition clinical trial was designed to evaluate the efficacy of three different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce lost to follow-up during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being lost to follow-up. RESULTS: During the study, intensive tracing efforts were initiated after the first 1686 mother-infant pairs had been enrolled, and 327 pairs were missing. Of these pairs, 60 were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the lost to follow-up rate was 3.4%. At study's end, 290 (12.2%) of the 2369 mother-infant pairs were lost to follow-up. Among successfully traced missing pairs, relocation was common and three were deceased. Log-binomial regression modeling revealed higher maternal hemoglobin and older maternal age to be significant predictors of perfect attendance. These factors and the presence of food insecurity were also significantly associated with lower rates of lost to follow-up. CONCLUSION: In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of lost to follow-up participants and were very effective in preventing further lost to follow-up during the remainder of the trial. The association between food insecurity and lower rates of lost to follow-up is likely related to the study's provision of nutritional support, including a family maize supplement, which may have contributed to patient retention.

Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants.

BACKGROUND & AIMS: The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naïve, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. METHODS: Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14 weeks of age. RESULTS: One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48 weeks of age.HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were <4 log10 IU/ml compared to ⩾ 8 log10 IU/ml in three infants of mothers who did not. CONCLUSIONS: HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses.

Changes in soluble transferrin receptor and hemoglobin concentrations in Malawian mothers are associated with those values in their exclusively breastfed, HIV-exposed infants.

Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 × 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR ß = -0.18 mg/L, P < 0.001; hemoglobin ß = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736.

Role of intestinal mucosal integrity in HIV transmission to infants through breast-feeding: the BAN study.

BACKGROUND: Increased intestinal permeability may be one of the mechanisms of transmission of human immunodeficiency virus (HIV) to infants through breast-feeding. Intestinal permeability correlates with microbial translocation, which can be measured through quantification of bacterial lipopolysaccharide (LPS). METHODS: We evaluated levels of plasma LPS (by the Limulus amebocyte lysate assay) and immune activation markers in serial specimens from infants exposed to but uninfected with HIV and infants infected with HIV from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study. RESULTS: Plasma LPS levels increased after infants in the BAN study were weaned from the breast, at 24 weeks of age. Cotrimoxazole prophylaxis was associated with higher plasma LPS levels (P = .004). Infants with HIV infection had higher LPS levels, compared with uninfected infants (P = .004). Higher preinfection plasma LPS levels were a significant predictor of infant HIV infection through breast-feeding (hazard ratio = 1.60 for every unit increase in plasma LPS level; P = .01) and of lower infant length-for-age z scores (P = .02). CONCLUSIONS: These findings suggest that disruption in intestinal integrity is a mechanism of HIV transmission to infants through breast-feeding. Weaning from breast milk and use of antibiotic prophylaxis was associated with increased levels of microbial translocation, which could facilitate HIV entry through the intestine. Complementary approaches to enhance intestinal mucosal integrity in the infant may further reduce breast-feeding transmission of HIV.