Browsing by Author "Chinula, Lameck"

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    Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study
    (Msphere, 2019) Hompe, Eliza D.; Jacobson, Denise L.; Eudailey, Joshua A.; Butler, Kevin; Edwards, Whitney; Pollara, Justin; Brummel, Sean S.; Fouda, Genevieve G.; Chinula, Lameck; Kamanga, Melvin; Kinikar, Aarti; Moodley, Dhayendre; Owor, Maxensia; Fowler, Mary Glenn; Permar, Sallie R.
    To design immune interventions that can synergize with antiretroviral therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential to characterize maternal immune responses in the setting of ART during pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported an association between breast milk envelope (Env)-specific antibodies and antibodydependent cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In this study, we investigated whether these immune correlates were similarly associated with protection in a matched case-control study of mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding in the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression models adjusted for maternal plasma viral load. The odds ratios of postnatal MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval [CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI, 0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and 4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor in untreated HIV-infected women, there was a strong correlation between the magnitudes of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the small number of postnatal virus transmissions in the landmark PROMISE study, no single antibody response was associated with breast milk transmission risk.
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    Pregnancy outcomes of women conceiving on antiretroviral therapy (ART) compared to those commenced on ART during pregnancy.
    (Clinical Infectious Diseases, 2021) Theron, Gerhard; Brummel, Sean; Fairlie, Lee; Pinilla, Mauricio; McCarthy, Katie; Owor, Maxensia; Chinula, Lameck; Makanani, Bonus; Violari, Avy; Moodley, Dhayendre; Chakhtoura, Nahida; Browning, Renee; Hoffman, Risa; Glenn Fowler, Mary
    Globally, the number of HIV-infected women of child-bearing age conceiving on ART is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The PROMISE 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Methods The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of non-breastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who re-started ART after pregnancy was diagnosed. Results Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (<2500gm) for women who conceived while on ART {relative risk 2.65 (95% CI 1.20, 5.81)}, and also a higher risk of spontaneous abortion, stillbirth, or neonatal death {hazard ratio 1.40 (0.99, 1.98)} compared to women who re-started ART after they were found to be pregnant during trial follow up. Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa805/5860458 by guest on 22 June 2020 Accepted Manuscript Conclusions We found an increased risk for adverse pregnancy outcomes in women conceiving on ART emphasising the need for improved obstetric and neonatal care for this group.
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    Unintended pregnancy and contraception use among African women living with HIV: Baseline analysis of the multi-country US PEPFAR PROMOTE cohort
    (Public Library of Science, 2024-03-11) Aizire, Jim; Yende-Zuma, Nonhlanhla; Hanley, Sherika; Nematadzira, Teacler; Nyati, Mandisa M; Dadabhai, Sufia; Chinula, Lameck; Nakaye, Catherine; Fowler, Mary Glenn; Taha, Taha
    About 90% of unintended pregnancies are attributed to non-use of effective contraception-tubal ligation, or reversible effective contraception (REC) including injectables, oral pills, intra-uterine contraceptive device (IUCD), and implant. We assessed the prevalence of unintended pregnancy and factors associated with using RECs, and Long-Acting-Reversible-Contraceptives (LARCs)-implants and IUCDs, among women living with HIV (WLHIV) receiving antiretroviral therapy (ART). We conducted cross-sectional analyses of the US-PEPFAR PROMOTE study WLHIV on ART at enrollment. Separate outcome (REC and LARC) modified-Poisson regression models were used to estimate prevalence risk ratio (PRR) and corresponding 95% confidence interval (CI). Of 1,987 enrolled WLHIV, 990 (49.8%) reported their last/current pregnancy was unintended; 1,027/1,254 (81.9%) non-pregnant women with a potential to become pregnant reported current use of effective contraception including 215/1,254 (17.1%) LARC users. Compared to Zimbabwe, REC rates were similar in South Africa, aPRR = 0.97 (95% CI: 0.90-1.04), p = 0.355, lower in Malawi, aPRR = 0.84 (95% CI: 0.78-0.91), p<0.001, and Uganda, 0.82 (95% CI: 0.73-0.91), p<0.001. Additionally, REC use was independently associated with education attained, primary versus higher education, aPRR = 1.10 (95% CI: 1.02-1.18), p = 0.013; marriage/stable union, aPRR = 1.10 (95% CI: 1.01-1.21), p = 0.039; no desire for another child, PRR = 1.10 (95% CI: 1.02-1.16), p = 0.016; infrequent sex (none in the last 3 months), aPRR = 1.24 (95% CI: 1.15-1.33), p<0001; and controlled HIV load ([less than or equal to] 1000 copies/ml), PRR = 1.10 (95% CI: 1.02-1.19), p = 0.014. LARC use was independently associated with country (Zimbabwe ref: South Africa, PRR = 0.39 (95% CI: 0.26-0.57), p<0.001; Uganda, PRR = 0.65 (95% CI: 0.42-1.01), p = 0.054; and Malawi, aPRR = 0.87 (95% CI: 0.64-1.19), p = 0.386; HIV load ([less than or equal to] 1000 copies/ml copies/ml), aPRR=1.73 (95% CI: 1.26-2.37), p<0.001; and formal/self-employment, aPRR = 1.37 (95% CI: 1.02-1.91), p = 0.027. Unintended pregnancy was common while use of effective contraception methods particularly LARCs was low among these African WLHIV. HIV viral load, education, sexual-activity, fertility desires, and economic independence are pertinent individual-level factors integral to the multi-level barriers to utilization of effective contraception among African WLHIV. National programs should prioritize strategies for effective integration of HIV and reproductive health care in the respective African countries.