Cost and cost-effectiveness of transitioning to universal initiation of lifelong antiretroviral therapy for all HIV-positive pregnant and breastfeeding women in Swaziland.

OBJECTIVES: To assess the costs and cost-effectiveness of transitioning from antiretroviral therapy (ART) initiation based on CD4 cell count and WHO clinical staging ('Option A') to universal ART ('Option B+') for all HIV-infected pregnant and breastfeeding women in Swaziland. METHODS: We measured the total costs of prevention of mother-to-child HIV transmission (PMTCT) service delivery at public sector facilities with empirical cost data collected at three points in time: once under Option A and again twice after transition to the Option B+ approach. The cost per woman treated per month includes recurrent costs (personnel, overheads, medication and diagnostic tests) and capital costs (buildings, furniture, start-up costs and training). Cost-effectiveness was estimated from the health services perspective as the cost per woman retained in care through 6 months postpartum. This analysis is nested within a larger stepped-wedge evaluation, which demonstrated a 26% increase in maternal retention after the transition to Option B+. RESULTS: Across the five sites, the total cost for PMTCT during the study period (from August 2013 to October 2015, in 2015 US$) was $868,426 for Option B+ and $680 508 for Option A. The cost per woman treated per month was $183 for a woman on ART under Option B+, and $127 and $118 for a woman on ART and zidovudine (AZT), respectively, under Option A. The weighted average cost per woman treated on Option B+ was $826 compared to $525 under Option A. The main cost drivers were the start-up costs, additional training provided and staff time spent on PMTCT tasks for Option B+. The incremental cost-effectiveness ratio was estimated at $912 for every additional mother retained in care through six months postpartum. CONCLUSIONS: The cost and cost-effectiveness outcomes from this study indicate that there is a robust economic case for pursuing the Option B+ approach in Swaziland and similar settings such as South Africa. Furthermore, these costs can be used to aid decision making and budgeting, for similar settings transitioning to test and treat strategy.

Burden of tuberculosis in HIV-positive pregnant women in Cape Town, South Africa.

BACKGROUND: The burden of active tuberculosis (TB) in pregnancy compared with preconception and postpartum is unclear, particularly with universal antiretroviral therapy (ART) initiation in pregnancy. METHODS: We retrospectively compared active TB incidence in the 18 months preconception, during pregnancy and up to 6 months postpartum in human immunodeficiency virus (HIV) positive women attending antenatal care at a primary health care facility in Cape Town from 2013 to 2014. RESULTS: Among 1513 women (4116 person-years [py]), 1489 (98.4%) received lifelong ART in pregnancy, and 79 TB episodes were identified. Unadjusted TB incidence rates (IR) preconception, during pregnancy and postpartum were 2466 (95%CI 1863-3202), 1127 (95% CI 600-1928) and 1447 (95% CI 694-2661) per 100 000 py, respectively. Adjusting for age and CD4 count at first antenatal visit and ART status, TB risk was lower during pregnancy (incidence rate ratio [IRR] 0.17 vs. preconception, 95%CI 0.09-0.31) and increased slightly postpartum (IRR 1.31 vs. pregnancy, 95%CI 0.56-3.07). CONCLUSION: Among HIV-positive women in South Africa, the TB burden preconception, during pregnancy and postpartum was substantial. The risk of TB during pregnancy was lower than preconception, but increased slightly postpartum; this represents missed opportunities for diagnosis, prevention and control. Improved TB prevention strategies and integrated care for HIV-positive women and their children are needed.

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

'There's no place like home': perceptions of home-based HIV testing in Lesotho.

HIV testing has the potential to reduce HIV transmission by identifying and counseling individuals with HIV, reducing risk behaviors, linking persons with HIV to care and earlier treatment, and reducing perinatal transmission. In Lesotho, a high HIV prevalence country in which a large proportion of the population has never tested for HIV, home-based testing (HBT) may be an important strategy to increase HIV testing. We identified factors influencing acceptability of HIV prevention strategies among a convenience sample of 200 pregnant or post-partum Basotho women and 30 Basotho men. We first conducted cross-sectional surveys, followed by key informant interviews with all 30 men and focus group discussions with a sub-set of 62 women. In total, 82% of women reported positive perceptions of HBT; women and men viewed HBT as a potential way to increase testing among men and saw the home as a comfortable, supportive environment for testing and counseling couples and families together. Potential barriers to HBT uptake included concerns about confidentiality, privacy, coercion to test, conflict within the family and fear of HIV/AIDS-associated stigma. Participants emphasized community mobilization and education as important elements of HBT.

Patient selection and results of cardiac transplantation in patients with cardiomyopathy.

Cardiac transplantation for the treatment of end-stage congestive heart failure has been shown to be of benefit regardless of the etiology. With few exceptions, the evaluation of patients with end-stage heart failure is the same, regardless of the etiology. In those with cardiomyopathy not as a result of CAD, special attention must be given to exclude secondary causes of cardiomyopathy such as amyloidosis, hemochromatosis, and sarcoidosis, as well as generalized systemic illnesses that may also involve the heart, either secondary or hereditary, because special consideration must be given to these patients on a case-by-case basis to determine that there is no general systemic involvement of the illness that would preclude satisfactory rehabilitation after transplantation. Before cardiac transplantation becomes widely available, there must be a greater number of donor hearts, the lack of which now severely limits the number of transplants performed in comparison with the estimated need.66 Additionally, more effective and specific immunosuppressive agents must be identified in order to reduce the incidence of rejection, infection, and accelerated atherosclerosis that now limits the longevity of transplant recipients. Furthermore, the ideal immunosuppressive agent should be associated with fewer side effects than those currently available. The emotional and economic burdens placed on the patient, the family, and society must be balanced against the benefits generated by the procedure. Despite these limitations, cardiac transplantation continues to offer hope for the terminally ill patient, which must be tempered by an understanding of the real limitations of transplantation.

Immunomodulation of intradermal mammary carcinoma using staphage lysate in a rat model.

Staphage lysate (SPL), a preparation of Staphylococcus aureus obtained by bacteriophage lysis, is an interferon-inducer and stimulator of T and B lymphocytes. Does SPL, as an immunopotentiator, have an effect on the growth and metastases of an intradermal mammary carcinoma? To answer this question, a study using SPL in female Fischer rats injected with 7 x 10(6) viable 13762 mammary tumor cells on the midback were used. Four groups were created with 10 animals in each group. Group I was the control group. They received no treatment. Group II received 0.3 ml of medium in which SPL was carried on alternate days. Group III received 0.3 ml SPL on alternate days. Group IV were sensitized with dead staphylococcal organisms prior to SPL treatment as in Group III. Tumor diameters were recorded on days 10, 13, 17, and 21, and autopsies were performed to determine the extent of metastases. Histologic examination and serum antibody measurements were performed. The mean tumor diameters on day 21 were: Group I: 4.1 +/- 0.2 cm; Group II: 3.80 +/- 0.19 cm; Group III: 3.04 +/- 0.13 cm; and Group IV: 2.97 +/- 0.14 cm. Rats receiving SPL treatment in Groups III and IV had significantly smaller tumors (P less than .001). The incidence of axillary lymph node involvement was: Group I: 100%; Group II: 87.5%; Group III: 62.5%; and Group IV: 40%. Lung metastases were seen in all groups. Groups I and II had 100% incidence of grossly visible nodules, whereas Groups III and IV had 75% and 70% involvement. Gross findings were confirmed by microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the nature of the flap/bed interaction in rodents--Part II: Morphological and fluorescein kinetic data.

The current study in rats concerns two aspects of the flap/bed interaction: fluorescein kinetics and histological finding. In the control group of animals in the fluorescein kinetics experiment, flaps were raised and then reattached. In one experimental group, the flaps were raised and placed on a sterile polyethylene film. In two other groups, the flaps were raised and then the pedicle was cut, either immediately or at specific intervals. At intervals up to 24 hours several animals were injected with 5% fluorescein. In the control group fluorescein penetration increased with time, while it decreased in the polyethylene-film group. There was virtually no fluorescein staining in both cut-pedicle groups. To study histological events, the animals were divided into groups with flaps and groups in which the distal end of each flap was severed to form a contiguous skin graft. Other conditions were varied. All flaps were cultured, and biopsy specimens were obtained from three areas at several time intervals. Histological sections from the distal flap were markedly different from the corresponding skin grafts. These results corroborate previously noted survival rates.

[Contributions to the liberation of drugs from suspension ointments. Part 12: On the suitability of some synthetic hydrophobic membranes for liberation studies (author's transl)]. / Beiträge zur Arzneistoffliberation aus Suspensionssalben. 12. Mitteilung: Zur Eignung einiger künstlicher hydrophober Membranen für Liberationsuntersuchungen.

The release rates determined for various salicylic acid and prednisolone ointments on using different membranes in the in vitro model according to Horsch and Kögel [20] were compared with one another in regard to possible membrane-specific differences in liberation kinetics and in validity. The results obtained with salicylic acid ointments by the lipophil collodion-lipid membranes and silicone membranes developed by Fürst and coworkers [14] were comparable with those yielded by the hydrophilic cellulose membrane: release rates of comparable order of magnitude; same order of ranking of the bases used; plots of the cumulated percentages of release against the root of time providing no evidence of differences in kinetics. In contrast, the permeability of a further hydrophobic membranes (silicone, polyester) was markedly lower. As to the prednisolone ointments, the collodion-lipid membranes yielded comparable release rates and orders of ranking when the drug was incorporated into hydrophilic bases, whereas the silicone membrane was considerably inferior in permeability.