Randomised placebo-controlled trial to evaluate the effect of vitamin A on mother-to-child transmission of HIV-1 in Bloemfontein

Abstract

English: Mother-to-child (vertical) transmission is the primary means by which young children acquire human immunodeficiency virus type 1 (HIV -1) infection. Anti-retrovirals such as Zidovudine and nevirapine can reduce vertical transmission of HIV significantly, but this treatment is still largely unaffordable in Africa. Maternal vitamin A deficiency is suspected to enhance vertical transmission of HIV. Furthermore, vitamin A is known to act as a coenzyme to the immune process. Therefore, a double-blind randomized placebo controlled trial to assess the effect of vitamin A supplementation on vertical transmission of HIV was launched in Bloemfontein in 1997. A total of 2949 pregnant women attending the antenatal clinics at Pelonomi and Universitas hospitals and the Mangaung University Community Partnership clinic were counselled for HIV testing, and 2543 were willing to be screened by HIV testing for possible inclusion in the trial. Of the women screened 595 (23.4%) were HIV positive, and 303 of these were willing to participate in the trial. 152 women were randomized to vitamin A treatment and 151 to placebo treatment. Patients were seen at 2 monthly intervals in the antenatal phase. Post-natally mother-infants pairs were seen when the infant was 1 month old, 3 months old, and thereafter, 3 monthly till 18 months old. A total of 191 patients (63% of all the study participants) missed one or more visits and had to be traced. Of the 303 patients included in the study 158 had a conclusive infant HIV test result (patients in the Intention To Treat (!TT) analysis population) and 104 patients had a conclusive infant mv test result when the baby was 3 months old (patients in the Per Protocol (PP) analysis population). Of 158 patients, in the ITT population 73 were in the vitamin A group and 85 in the placebo group. Per treatment group the baseline characteristics of those in the IIT population and those who are not, did not differ significanti y. The mv transmission rates were 19.2% and 21.2% for vitamin A and placebo groups respectively (IIT population). There is no statistically significant difference in the transmission rates between vitamin A and placebo groups (p=0.76). Overall, this study provides no evidence that vitamin A is effective in reducing vertical mv-1 transmission rate. There was no statistically significant difference in the percentages of mv symptoms recorded at post delivery visit 1 through to the 18 months visit between the two treatment groups for either mothers or infants. A similar pattern was observed for the vital signs for the mothers. The full blood and T-cell counts were similar between the two treatment groups at all visits for both mothers and infants. Only 4 patients reported adverse events; these were not related to the treatment. Twenty six infants and one mother died during the study. The overall infant mortality rate was 85.8 per 1000 infant population. The infant death rates were approximately 11% in the placebo group and 6% in the vitamin A group (p=0.097). Thus, Vitamin A was associated with a reduction in infant mortality, although not statistically significant. This association may be worth further investigation as there is potential for a substantial impact.

Afrikaans: Moeder-na-kind (vertikale) oordrag is die algemeenste mamer waarop Jong kinders menslike immuniteitsgebrek virus tipe 1 (MIV -1) opdoen. Antiretrovirale middels soos Zidovudine en nevirapine kan die vertikale oordrag van MIV betekenisvol verlaag, maar hierdie behandeling is steeds meestal nie bekostigbaar in Afrika nie. Daar word vermoed dat moederlike vitamine A gebrek die vertikale oordrag van MIV bevorder. Verder is dit bekend dat vitamine A 'n ko-ensiem is tot die immuunproses. Daarom is 'n gerandomiseerde dubbelblinde plasebo gekontrolleerde proef om die effek van vitamine A supplementasie op die vertikale oordrag van HIV te bepaal in 1997 in Bloemfontein van stapel gestuur. 'n Totaal van 2949 swanger vroue wat die voorgeboorteklinieke by die Universitas en Pelonomi Hospitale en die Mangaung University Community Partnership Project kliniek bygewoon het, het berading vir MIV-toetsing ontvang, en 2543 was bereid om deur MIVtoetsing gesif te word vir moontlike insluiting in die proef. Van die vroue wat gesif is, was 595 (23.4%) MIV-positief, en 303 van hulle het ingewillig om aan die studie deel te neem. 152 MIV positiewe vroue is gerandomiseer om vitamine A behandeling te ontvang en 151 plasebo behandeling. Pasiënte is tydens die voorgeboorte fase 2 maandeliks gesien. In die nageboorte fase is moeder-baba pare gesien toe die baba 1 maand oud was, 3 maande oud en daarna 3 maandeliks tot 18 maande oud. 'n Totaal van 191 pasiënte (63% van al die studiedeelnemers) het een of meer besoek gemis en moes opgespoor word. Van die 303 vroue wat ingesluit is in die studie, het 158 'n afdoende baba-MIV toetsuitslag gehad (pasiënte in die Beplan om te Behandel (BB) ontledingspopulasie) en 104 pasiënte het 'n afdoende baba MIV toetsuitslag gehad toe die baba 3 maade oud was (pasiënte in die Per Protokol (PP) ontledingspopulasie). Van die 158 pasiënte in die BB populasie was 73 in die vitamine A groep en 85 in die plasebo groep. Per behandelingsgroep was daar geen betekenisvolle verskille ten opsigte van die basislyngegewens tussen die vroue in die BB populasie en diegene nie in die BB nie. Die MIV oordragskoerse was 19.2% en 21.2% vir die vitamine A en plasebo groepe onderskeidelik (BB populasie). Daar was geen statisties betekenisvolle verskil in die oordragskoers tussen vitamine A en plasebo nie (p=0.76). Hierdie studie lewer geen bewys dat vitamine A effektief is in die verlaging van die vertikale oordragskoers nie. Daar was geen statisties betekenisvolle verskille tussen die twee groepe ten opsigte van die persentasies MIV simptome vir moeders of babas by die eerste nageboorte besoek tot by die 18 maande besoek nie. 'n Soortgelyke patroon is waargeneem vir die vitale tekens van die moeders. Die volbloed en T-sel tellings was soortgelyk tussen die behandelings vir alle besoeke vir moeders sowel as babas. Slegs 4 pasiënte het newe-effekte gerapporteer, en dit het nie verband gehou met die behandeling nie. Ses-en-twintig babas en een moeder het gedurende die studie gesterf. Die algehele babasterftekoers was 85.5 per 100 babas. Die babasterftekoers was ongeveer Il% in die plasebogroep en 6% in die vitamine A groep (p=0.097). Vitamine A is dus geassosieer met In verlaging in babasterftes, alhoewel nie statisties betekenisvol nie. Dit verdien verdere ondersoek aangesien die moontlikheid vir In groot impak bestaan.