Antiretroviral therapy refusal among newly diagnosed HIV-infected adults.

OBJECTIVE: To determine rates and predictors of treatment refusal in newly identified HIV-infected individuals in Soweto, South Africa. DESIGN: It is designed as a cross-sectional study. METHODS: We analyzed data from adult clients (>18 years) presenting for voluntary counseling and testing (VCT) at the Zazi Testing Center, Perinatal HIV Research Unit to determine rates of antiretroviral therapy (ART) refusal among treatment-eligible, HIV-infected individuals (CD4(+) cell count < 200 cells/µl or WHO stage 4). Multiple logistic regression models were used to investigate factors associated with refusal. RESULTS: From December 2008 to December 2009, 7287 adult clients were HIV tested after counseling. Two thousand, five hundred and sixty-two (35%) were HIV-infected, of whom 743 (29%) were eligible for immediate ART. One hundred and forty-eight (20%) refused referral to initiate ART, most of whom (92%) continued to refuse after 2 months of counseling. The leading reason for ART refusal was given as 'feeling healthy' (37%), despite clients having a median CD4(+) cell count of 110 cells/µl and triple the rate of active tuberculosis as seen in nonrefusers. In adjusted models, single clients [adjusted odds ratio (AOR) 1.80, 95% confidence interval (CI) 1.06-3.06] and those with active tuberculosis (AOR 3.50, 95% CI 1.55-6.61) were more likely to refuse ART. CONCLUSION: Nearly one in five treatment-eligible HIV-infected individuals in Soweto refused to initiate ART after VCT, putting them at higher risk for early mortality. 'Feeling healthy' was given as the most common reason to refuse ART, despite a suppressed CD4(+) count and comorbidities such as tuberculosis. These findings highlight the urgent need for research to inform interventions targeting ART refusers.

In utero and intra-partum HIV-1 transmission and acute HIV-1 infection during pregnancy: using the BED capture enzyme-immunoassay as a surrogate marker for acute infection.

OBJECTIVE: The BED assay was developed to estimate the proportion of recent HIV infections in a population. We used the BED assay as a proxy for acute infection to quantify the associated risk of mother-to-child-transmission (MTCT) during pregnancy and delivery. Design A total of 3773 HIV-1 sero-positive women were tested within 96 h of delivery using the BED assay, and CD4 cell count measurements were taken. Mothers were classified according to their likelihood of having recently seroconverted. METHODS: The risk of MTCT in utero and intra-partum was assessed comparing different groups defined by BED and CD4 cell count, adjusting for background factors using multinomial logistic models. RESULTS: Compared with women with BED ≥ 0.8/CD4 ≥ 350 (typical of HIV-1 chronic patients) there was insufficient evidence to conclude that women presenting with BED < 0.8/CD4 ≥ 350 (typical of recent infections) were more likely to transmit in utero [adjusted odds ratio (aOR) = 1.37, 96% confidence interval (CI) 0.90-2.08, P = 0.14], whereas women with BED < 0.8/CD4 200-349 (possibly recently infected patients) had a 2.57 (95% CI 1.39-4.77, P-value < 0.01) odds of transmitting in utero. Women who had BED < 0.8/CD4 < 200 were most likely to transmit in utero (aOR 3.73, 95% CI 1.27-10.96, P = 0.02). BED and CD4 cell count were not predictive of intra-partum infections. CONCLUSIONS: These data provide evidence that in utero transmission of HIV might be higher among women who seroconvert during pregnancy.

Significantly diminished long-term specificity of the BED capture enzyme immunoassay among patients with HIV-1 with very low CD4 counts and those on antiretroviral therapy.

OBJECTIVE: To estimate the proportion who test as recent infections by the BED capture enzyme immunoassay (BED) among patients about to commence, and those receiving, antiretroviral therapy. DESIGN: Cryopreserved plasma samples from HIV patients on the national antiretroviral treatment (ART) rollout program at Tygerberg Hospital HIV clinic, South Africa, were tested using the BED assay. PARTICIPANTS: Five hundred five patients qualifying for ART were included in this study. METHOD: All plasma samples from each patient were tested by BED. Basic demographic data, HIV-1 viral load, and CD4 count results were obtained from the laboratory database. MAIN OUTCOME: The proportion presenting as false recently infected is reported. RESULTS: Among patients, with presumed long-term HIV-1 infections, about to commence ART, 11.2% [95% confidence interval (CI): 8.3 to 14.5%] tested recent by BED. The proportion was higher among patients with CD4 counts < 50 cells per microliter [odds ratio 2.63, 95% CI: 1.39 to 5.00] and log10 HIV-1 viral load less than 4 [odds ratio 3.03, 95% CI: 1.05 to 9.09]. Proportions testing false recent increased from 11.2% before ART to 17%, 25%, 38%, and 56% at 0.5, 1, 1.5, and 2 years, respectively, after ART initiation. CONCLUSIONS: If the BED method is to be used for the accurate estimation of HIV incidence from cross-sectional surveys, it will be essential, before other statistical adjustment methods, to identify, at least, all cases who are on ART and all those with CD4 counts < 50 cells per microliter. The more general remaining problem is the unequivocal identification of all persons with long-term HIV infections.

The impact of safer breastfeeding practices on postnatal HIV-1 transmission in Zimbabwe.

OBJECTIVES: We assessed the association between exposure to an educational intervention that emphasized safer breastfeeding practices and postnatal HIV transmission among 437 HIV-positive mothers in Zimbabwe, 365 of whom did not know their infection status. METHODS: Mothers were tested for HIV and were encouraged--but not required--to learn their HIV status. Intervention exposure was assessed by a questionnaire, Turnbull methods were used to estimate postnatal HIV transmission, and multivariate Cox proportional hazard models were constructed to assess the association between intervention exposure and postnatal HIV transmission. RESULTS: Cumulative postnatal HIV transmission was 8.2%; each additional intervention contact was associated with a 38% reduction in postnatal HIV transmission. HIV-positive mothers who were exposed to both print and video materials were 79% less likely to infect their infants compared with mothers who had no exposure. These findings were similar for mothers who did not know their HIV status. CONCLUSIONS: The promotion of exclusive breastfeeding has the potential to reduce postnatal HIV transmission among women who do not know their HIV status, and child survival and HIV prevention programs should support this practice.

Effects of infant sex on mother-to-child transmission of HIV-1 according to timing of infection in Zimbabwe.

We examined the relationship between sex and the risk of intrauterine, intrapartum and postnatal HIV transmission among 4495 infants born to HIV-infected mothers in Harare, Zimbabwe. Intrauterine transmission was 8.6%, and consistent with other studies was higher among girl than boy infants (AOR 1.53; 95% CI 1.23-1.91). Unlike previous studies, we observed no independent effect of infant sex on intrapartum or breastfeeding-associated HIV transmission. Sex-specific postnatal prevention strategies are not warranted in this population.

Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality.

BACKGROUND: Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants. METHODS: A total of 14,110 mother-infant pairs were enrolled < or =96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 x 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis. RESULTS: Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) positive [corrected] for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P=.01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ~2-fold higher mortality (P< or =.05). CONCLUSIONS: Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas.

Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival.

OBJECTIVES: The promotion of exclusive breastfeeding (EBF) to reduce the postnatal transmission (PNT) of HIV is based on limited data. In the context of a trial of postpartum vitamin A supplementation, we provided education and counseling about infant feeding and HIV, prospectively collected information on infant feeding practices, and measured associated infant infections and deaths. DESIGN AND METHODS: A total of 14 110 mother-newborn pairs were enrolled, randomly assigned to vitamin A treatment group after delivery, and followed for 2 years. At baseline, 6 weeks and 3 months, mothers were asked whether they were still breastfeeding, and whether any of 22 liquids or foods had been given to the infant. Breastfed infants were classified as exclusive, predominant, or mixed breastfed. RESULTS: A total of 4495 mothers tested HIV positive at baseline; 2060 of their babies were alive, polymerase chain reaction negative at 6 weeks, and provided complete feeding information. All infants initiated breastfeeding. Overall PNT (defined by a positive HIV test after the 6-week negative test) was 12.1%, 68.2% of which occurred after 6 months. Compared with EBF, early mixed breastfeeding was associated with a 4.03 (95% CI 0.98, 16.61), 3.79 (95% CI 1.40-10.29), and 2.60 (95% CI 1.21-5.55) greater risk of PNT at 6, 12, and 18 months, respectively. Predominant breastfeeding was associated with a 2.63 (95% CI 0.59-11.67), 2.69 (95% CI 0.95-7.63) and 1.61 (95% CI 0.72-3.64) trend towards greater PNT risk at 6, 12, and 18 months, compared with EBF. CONCLUSION: EBF may substantially reduce breastfeeding-associated HIV transmission.