Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate ...antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov , number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197–249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52–1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43–0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28–0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5–27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5–32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group. Interpretation Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment. Funding US National Institute of Allergy and Infectious Diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean ...delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. STUDY DESIGN: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. RESULTS: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 95% confidence interval, 1.05–1.29), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). CONCLUSION: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND: Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination ...antiretroviral therapy. OBJECTIVE: We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. STUDY DESIGN: Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. RESULTS: A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77–1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88–1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23–2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11–1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77–4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80–1.04). CONCLUSION: In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and ...treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity. OBJECTIVE: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission. STUDY DESIGN: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression. RESULTS: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35–8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77–23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07–4.58), and maternal nontreponemal titers ≥1:64 (1.09–1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59–1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02–1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17–1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55–0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection. CONCLUSION: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination ...antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women.
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